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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.