The Christodora is home to Milly and Jared, a privileged young couple with artistic ambitions. Their neighbour, Hector, a Puerto Rican gay man who was once a celebrated AIDS activist but is now a lonely addict, becomes connected to Milly's and Jared's lives in ways none of them can anticipate. Meanwhile, the couple's adopted son, Mateo, grows to appreciate the opportunities for both self-realization and oblivion that New York offers.

As the junkies and protestors of the 1980s give way to the hipsters of the 2000s and they, in turn, to the wealthy residents of the crowded, glass-towered city of the 2020s, enormous changes rock the personal lives of Milly and Jared and the constellation of people around them. Moving kaleidoscopically from the Tompkins Square Riots and attempts by activists to galvanize a response to the AIDS epidemic, to the New York City of the future, Christodora recounts the heartbreak wrought by AIDS, illustrates the allure and destructive power of hard drugs, and brings to life the ever-changing city itself.