After being infected with a hallucinogen, Sydney starts to lose touch with reality. Vaughn and Jack must rush to find an antidote before Sydney puts her life - and others next to her - into danger.

Sloane temporarily steps down as Director of his Task Force and gives Jack full authority over the next assignment, which involves Anna Espinosa, Sydney's old foe. However, Anna turns the tables on APO when she captures Nadia and forces Sydney to do her biddings. Sydney tells Nadia about the Rambaldi's prophecy which dictates that two sisters will fight and only one will survive. Meanwhile, Vaughn visits Sark and tries to trick him into helping them to catch Anna. In the end, one of the sisters is mortally wounded by Anna.

While Nadia is in a coma, Sark is taken into APO to help them infiltrate Cadmus Revolutionary Front and retrieve the bomb, but in return he demands to see Lauren's corpse and that Vaughn opens her coffin for him. Nadia may be the only person with the intel they need to intercept the bomb, so Jack is forced to prematurely wake Nadia from her coma, endangering her life, which doesn't please Sloane when he finds out.