Erica works with new allies to uncover a biological threat they suspect the Visitors have been plotting. Aboard the mothership, Anna meets with a special guest, while managing the investigation into the murder of a V. Chad does a segment on the V Healing Centers demonstrating their amazing medical abilities, but finds himself conflicted by some of his findings.

Erica, Ryan and Jack go on a harrowing mission to find the legendary John May in order to rescue Georgie. Anna brings Chad aboard the Mothership for a story on her Live Aboard Program and Tyler confronts his mom about his mysterious past.

Erica, Ryan, Father Jack and Hobbes learn Anna's sent a V shuttle filled with a deadly tracker team to find them, and must figure out how to stop the shuttle from landing. Meanwhile, Anna gives Tyler his invitation to the Live Aboard Program and Chad confronts Father Jack on what he knows about The Fifth Column.

The Season Two opener, "Red Rain," continues the action from last season's finale when Anna unleashed Red Sky on the planet. With the world on the brink of war and chaos all around, is there anyone who can stand up to Anna? Meanwhile, Ryan has been kept in isolation on the mothership, away from his hybrid baby so that Anna can experiment on her. Chad, seeking redemption for being used by Anna, now wants to fight with the Fifth Column, and Erica goes on a journey to find a scientist who can give her the answers to what Red Sky is, and where she learns the horrifying secret of what the Vs are doing on our planet.

After the radical faction of the Fifth Column murders three Peace Ambassadors, Erica goes on a mission to hunt down their leader, Eli Cohn, a former Mossad agent. Meanwhile, as Jack and other priests around the globe begin to speak out against the Visitors, Anna heads to the Vatican in an effort to convince the leaders of organized religion that the Visitors truly are "of peace".

Erica, seeking revenge against Anna, heads to Hong Kong to carry out a mission to strike a lethal blow against Anna. Meanwhile, Anna learns that Tyler's phosphorous level is too low – even after the Red Rain – and he might become useless to her; and Lisa and Diana bond, beginning to form an alliance against Anna.

Anna is focused on having Lisa breed with Tyler to ensure the evolution of the Visitors, while Erica and Diana enlist Lisa to stage a coup against Anna and remove her from power before humanity is destroyed. Erica and the Fifth Column join Lisa in the attempted coup, which has devastating results. Also in the episode, Marc Singer, who played freedom fighter Mike Donovan on the original "V" series, guest stars as Lars Tremont, a member of a top secret organization of high-ranking military and government leaders from around the globe who have long suspected that the Visitors are very much not here in peace.