A break-in on Wisteria Lane leaves the neighbors feeling vulnerable, especially Susan, who reluctantly accepts a date with a persistent policeman after Mike appears indifferent to her. Rex takes the kids away for the weekend as a lonely Bree finds herself bonding with Zach. Meanwhile, Lynette and Tom pull out all the stops to get their uncontrollable twins Porter and Preston accepted at a prestigious private school, and the unexpected arrival of Carlos' mother puts a crimp in Gabrielle's covert love life.

Lynette locks horns with officious mom Maisy Gibbons at the twins' school who is trying to produce a "politically correct" play about "Little Red Riding Hood." Meanwhile, Susan continues to investigate the mystery of Zach's sudden disappearance. She soon finds out his father Paul put him in Seacrest, a mental institution. She and Julie then go to investigate.

Mama Solis comes closer to discovering Gabrielle's dirty little secret of her affair, and Bree comes undone when Rex suggests they hire a sex surrogate.

Susan and Edie decide to follow Mike and his houseguest Kendra on their night out together. Lynette becomes steadily more dependent on the twins' ADD medication. In the meantime Gabrielle becomes jealous of the "other" woman in John's life. And Bree's kids mutiny when they learn their dad has moved out. Tom is not happy when Lynette tries to take over his concept of new "Spotless Scrubs" to his clients.

In the aftermath of tragedy with Bree's son Andrew running over Carlos' mother Juanita Solis, the residents of Wisteria Lane take stock of their lives. Meanwhile, Susan grows suspicious of Mike's real reason for moving to the street. Lynette reaches the breaking point in her addiction to the twins' ADD medication as she tries other measures like acupuncture to release her stress. The mysterious Mr. Shaw gets down to business as he develops a relationship with Edie. Lastly, Gabrielle confesses her adulterous affair to a priest while Carlos' mother Juanita is in the hospital.

Looking to give her life a purpose, Gabrielle decides to organize a glamorous Halston fashion show for charity highlighting the ladies of Wisteria Lane. Bree and Rex are at odds on how to punish Andrew for putting Mrs. Solis in the hospital and finding drugs in his room. The police investigate a toy chest that Paul Young dumped in the river. Lastly, Lynette uses her business acumen to poach a nanny, Claire, but ends up getting involved between her current employer, Alexis.

The residents of Wisteria Lane all attend the unfortunate funeral of Juanita Solis as Carlos and Gabrielle fret over their financial and court issues. Lynette befriends a deaf woman, Alisa Stevens, whose children also attend Barcliff Academy with Porter and Preston, but her newfound friendship is quickly put to the test. Meanwhile, Bree encounters more trouble with her son Andrew when it comes to disciplining him and lastly, Susan finds herself attracted to Edie's hunky new contractor, but Edie doesn't want her to go with him as a favor to their fragile friendship.

Everything that begins must eventually end. This episode of beginnings and endings walks us both backwards and forwards as we take our final stroll down Wisteria Lane.