New York City experienced the first and largest HIV epidemic among injecting drug users (IDUs). Using data collected from IDUs entering the Beth Israel drug detoxification program, we trace the history of this epidemic from the mid-1970s through the early 2000s. The epidemic can best be described in terms of successive stages: (1) introduction and rapid transmission of HIV in the IDU population; (2) stabilization of HIV prevalence at a high level (over 50%); (3) a decline in incidence and prevalence, following large-scale implementation of syringe exchange programs; and (4) a sexual transmission phase, in which HIV prevalence is approximately equal among injecting and noninjecting heroin and cocaine users, and sexual transmission is more important than injecting-related transmission among IDUs. Given the current spread of HIV among IDUs in many places in the world, New York City provides a very strong example for implementation of large-scale comprehensive syringe exchange programs as early as possible in HIV epidemics among IDUs.