The episode picks up with the immediate aftermath of the Season 5 finale: Kate Beckett’s move to Washington D.C. for an FBI task force and her acceptance of Rick Castle’s marriage proposal. The "honeymoon phase" is quickly cut short when Castle, unable to resist meddling in Beckett’s new federal world, finds himself accidentally contaminated with a deadly, airborne chemical bioweapon.

: Back in New York, Alexis returns from Costa Rica with a new "fruitarian" boyfriend, Pi, adding a layer of comedic friction to the Castle household. Critical Perspective

: This marks the first time a Castle season premiere ended on a two-part cliffhanger.