In a riveting opening that picks up just moments after last season's climactic finale, Detective Beckett fights for her life as Castle, plagued by guilt over his role in the events, struggles to uncover who's behind her brutal shooting. Meanwhile, back at the precinct, Ryan and Esposito have to adjust, as Victoria "Iron" Gates becomes the precinct's new uncompromising Captain.

Gunshots, a fleeing van and a massive blood pool all point to murder, but when Castle & Beckett arrive at the crime scene, they discover that it lacks something - the victim! The investigation leads to the cutting-edge world of life-extension science, a cunning high-tech researcher (guest star William Atherton), and a sleazy porn mogul who invested in a modern-day "fountain of youth." Meanwhile, Alexis finds out whether she got into Stanford.