When the menace of Castor rears its head once more, Sarah and her entire family must come together to survive.

Castor pursues the Leda clones for original tissue samples. Helena, who is pregnant and imprisoned, is examined by a mysterious new villain. The Castor boys are also out to play, toying with a frightened young woman, Patty, in a sexy switcheroo that ultimately sets Sarah – and Art – hot on the Castor trail. But it’s not all fun and games for the Castor boys, as Sarah gleans they may have a mysterious defect that puts their lives in peril.

Leda and Castor are both on the hunt for original clone DNA. On-the-lam, Mark and Gracie pursue new leads to find the samples that might set them free, while Art and Sarah reunite to track them down. Meanwhile, Cosima and Scott try to learn more about Castor’s biology and Alison’s new money-making venture is going gangbusters. A shocking revelation about the Castor-Leda connection leaves the sisters reeling, just before Sarah witnesses a deadly Prolethean-Castor face-off.

Mark is taken down in a Prolethean shoot-out and Sarah must step in to help. But as Sarah gathers intel that puts her on the trail of the original Castor DNA, a familiar foe is not far behind. While Helena continues to toil in a faraway military compound, it is ultimately Sarah’s fate that will hang in the balance as she tries to save her sister. Meanwhile, Gracie is cast out from the Prolethean fold, and Alison and Donnie come face-to-face with unhappy drug lord, Jason Kellerman.

Helena and Sarah are reunited at the Castor camp. As Sarah suffers testing, Paul appears to chide her; but his allegiances are beginning to strain. While the Leda family worries about Sarah’s absence, Gracie ‘breaks loose’ under the care of Mrs. S and an unwilling Felix. Cosima falls hard for an internet date, Shay.

Paul digs and finds the ugly truth behind the Castor Boys’ logbooks of names, pushing him into action. Meanwhile, Felix is desperate for info on Sarah’s whereabouts, and presses the still-ailing Rachel for any shred of a lead. In order for Donnie and Alison to take their money-making endeavor to the “next level” she must introduce Jason Kellerman to her unique business plan.

Alison must secure a store front in order to take her and Donnie’s business to the “next level”. But things don’t go according to plan when her mother, Connie, proves to be a major hindrance. Cosima is facing familiar health issues and calls upon beleaguered Alison for a favor. But with Alison working to save an imperiled Donnie from the merciless hands of a drug lord, it’s Cosima who ends up doing a favor. An unassuming Scott gets closer to the greatest discovery of all, when he sits down with beleaguered clone Rachel.

When Rachel makes a promise to Sarah, it comes with a hefty price. Meanwhile, Helena and Gracie work with the Hendrixes, and Donnie takes Kellerman to task. Over at Castor, Coady and Benchman scheme to track down the Castor Original, and Rudy descends on DYAD for a much needed asset.

Sarah, Felix, and Mrs. S are in London to track down the Castor Original, but their enemies are not far behind.

Castor and Topside force Sarah to make uneasy alliances. But there is some rest for the wicked, when Donnie gives Helena an unexpected ‘gift’, and the results of Alison’s candidacy finally come in. Even as team Leda takes a moment to breathe, change is afoot and a life hangs in the balance.

After two months of respite, Sarah’s hard-won refuge in Iceland is shattered by a Neolution attack. Once again forced to flee, she realizes no matter how far her family runs it will never be far enough.

After evading a Neolution attack in Iceland, Sarah returns home to track down an elusive new ally. As Cosima struggles with Delphine’s disappearance, Alison and Donnie host a pregnant and ever-hungry Helena. Meanwhile Felix, feeling like an outsider, embarks on his own journey of self-discovery.

As Sarah reels from the shocking discovery of Neolution’s biotech, she’s desperate to find answers. Rachel receives a visit from her keeper and takes a fraught step forward towards recovery. Meanwhile, Helena is mistaken for “Mrs. Hendrix” when she answers a visit from suspicious visitors.

Sarah realizes her goals have aligned with her once enemy and forms a precarious alliance in hopes of getting to the head of Neolution. Meanwhile, on her end, Alison dispatches Felix and Donnie to infiltrate a Neolution fertility clinic that Beth investigated. Back at the lab, Cosima and Scott receive a revolting delivery from Alison. As Rachel grows closer to Charlotte, Susan Duncan leaves a devastating decision in her hands.

Sarah’s day off to reconnect with Kira quickly turns into a sleuthing mission aimed squarely at discrediting Felix’s new ties. Cosima steps up with Donnie to further investigate the Neolutionist fertility research center. While Donnie bumps into an all too familiar face, Cosima makes a shocking discovery that leads her into a dangerous encounter.

When Cosima admits doubts about finding a cure in time to save her life, Sarah makes a lone decision that exposes Kendall to those she’s spent years hiding from. Meanwhile, Art and Felix team up to protect naïve clone, Krystal Godderitch, from herself.

Sarah regresses to old habits while struggling to cope with the consequences of her decisions —reconnecting with Beth on a dark night of the soul. Back at the lab, Cosima, haunted by vicious memories and news of Delphine, attempts a dangerous Hail Mary to find a cure. At the Hendrixes, Alison is more determined than ever to create normalcy for her kids. As she forges ahead with a birthday party, Donnie is caught in the Neolution crosshairs.

As Alison is terrified by Neolution threats made against Donnie, Sarah and Mrs. S question her loyalty to her sisters. While Sarah is distracted, Siobhan sneaks out to seek vengeance. Meanwhile, Cosima and Susan Duncan work together in a final attempt to discover a cure.

With Susan Duncan deposed, Sarah finds herself in the same position as Rachel — under the heel of a new HBIC — causing the archenemies to come together for the greater good. Cosima and Susan butt heads on the ethical implications of human experiments. Meanwhile, when the Hendrixes' legal counsel, Adele, further investigates Donnie’s case, she begins to suspect Felix is keeping deep secrets. Helena’s arrival forces Felix to make a difficult decision.

When communication with Cosima is cut off and Neolution appears to be within striking distance, Sarah's alliance with Rachel goes out the window. Sarah lures a high-level Neolutionist into a trap, and sets out to bring down Neolution once and for all.

Sarah is deeply wounded and struggling to stay alive on the Island. Driven deep into its forest by Neolutionists and worse, she strives to make it far enough to rescue Cosima. Meanwhile, a recovering Cosima reunites with Delphine, but there's way more going on on this Island than Cosima imagined and Delphine can't give her all the answers she needs. What is clear is that Rachel is now firmly in charge as the right-hand of the 170-year-old founder of Neolution, P. T. Westmorland. Back home, Neolution puts the screws to Alison and Donnie in their hunt for Helena. The sestras couldn't be further apart when they need most to be together.

Captured by Neolution Sarah receives a damning ultimatum from Rachel: come into the fold, or lose your family. Her decision causes a clash with Kira who begins exploring her own maturity. Meanwhile, Ferdinand struggles to get a handle on Rachel's new velvet glove mandate in pursuit of the clones. With Neolutionists and Ferdinand watching their every move, Felix brings an old ally into the mix to help his family get Kira to safety. On the Island, Cosima struggles to comprehend the reality of the Neolution myth made real.

Stuck on the sidelines with Neolutionists crawling all over her home, Alison seeks to return to her community center, but Bailey Downs has moved on from her. As she flounders to take back some semblance of control, the ghost of friendships' past rears its handsome head. Art and his new partner show up at the Hendrix residence to continue their search for Helena, forcing Art to make a difficult moral judgement.

Following up on intel from a mysterious source, Mrs. S heads on the road with Sarah to investigate a lead on a Neolution defector. Meanwhile, an unexpected reunion takes place on the island, while Cosima's research leads her to a discovery more terrible than she could have ever imagined. As more pieces slide into place, the puzzle only seems to become more complicated.

While Sarah and Kira spend some well-needed bonding time at home, secrets are unlocked about Kira’s special gifts that are surprisingly linked to the island’s creature. Meanwhile, Cosima joins Delphine at the mansion for a twisted family dinner, causing a dangerous showdown with the Neolution patriarch.

Cosima is forced into an alliance when an old enemy returns to the island, accelerating P. T. Westmorland's sinister agenda. Meanwhile, on the mainland, Krystal stumbles onto a vital clue to the Neolution endgame. Sarah and Mrs. S’s research into Neolution's corporate ties leads to the cosmetics industry and an inevitable cross with Krystal Goderitch. But before Sarah can dig deeper, Krystal hijacks the investigation.

As P. T. Westmorland demands a more aggressive action on Kira, and Sarah fights to save her daughter, Rachel discovers a dark secret that makes her question her place within Neolution. Meanwhile, Cosima has returned with a vital clue to Westmorland's true identity.

Mrs. S orders the sisters to take a night off from sleuthing to celebrate Felix's art opening. But while Felix attempts to impress a famous gallerist with the help of his sestras, Sarah remains on edge with a nagging suspicion that S is hiding something. Meanwhile, wounded and desperate, Rachel reunites with an old ally, but their plans for revenge on Neolution put Clone Club in the line of fire.

A devastating loss is eclipsed when word reaches Sarah that Helena has been kidnapped. Clone Club bands together in a race against time, determined to find her before she has her babies. And with time running out, Sarah is forced into action in a last-ditch effort to save her sestra.

With Helena forced to take shelter behind enemy lines, it’s a bloody last stand for survival as Sarah and Art struggle to protect her, and end the siege on the sestras once and for all.