Refusing to collaborate with Dr. Zinberg on blood-transfusion research, an increasingly paranoid Thackery pushes himself to the limit, and beyond, in an effort to "solve the riddle" and beat his rival. Cornelia and Edwards arrive at a crossroads; Barrow trades one creditor for another; Lucy requests Bertie's help. With the Knick in the midst of yet another crisis, Robertson calls for a vote.
The setting: downtown New York in 1900, a tumultuous time of massive change and great progress. The series centers around the groundbreaking surgeons, nurses and staff at Knickerbocker Hospital, who are pushing the bounds of medicine in a time of astonishingly high mortality rates and zero antibiotics.