OBJECTIVE Acquired immunodeficiency syndrome (AIDS) was formally identified among injecting drug users (IDUs) in 1981, and research on preventing human immunodeficiency virus (HIV) infection among drug injectors began shortly thereafter. At the time this research was begun, there was a general assumption that drug user (who were called drug abusers at that time) were too self-destructive and their behavior too chaotic for them to change their behavior to avoid infection with HIV. This chapter reviews the history of research on implementation of programs for prevention of HIV infection among IDUs. METHODS Reviews of both research and program implementation research were conducted. Consultative discussions of issues and findings were conducted with researcher in the United States and other countries. RESULTS An extremely large amount of useful information has accumulated during the pat 15 years. We now know that the great majority of IDUs will change their injecting behavior in response to the threat of AIDS and that these behavior changes are effective in reducing HIV transmission among drug injectors. Additional insight is needed regarding the apparent insufficiency of some prevention programs to control HIV, the transmission dynamics of rapid HIV spread, and the persistence of moderate to high incidence of HIV infection in high seroprevalence populations. Despite the current research knowledge base, implementation of effective prevention programs in may countries is nonexistent to incomplete. CONCLUSIONS The most important barrier to reducing HIV transmission among drug injectors is not a lack of knowledge but the failure to implement effective prevention programs in may parts of the world.