During the initial phases of the HIV epidemic, epidemiological and prevention initiatives included a necessary focus on injection drug use which targeted, for the most part, heroin injectors. More recently, cocaine users have become a central focus for many HIV prevention interventions. This illustrates how researchers and public health practitioners have adapted to the changing and intersecting epidemics of HIV and drug abuse in order to more efficiently prevent the spread of HIV among drug abusers. In this special issue of Drug and Alcohol Dependence, the contributing authors focus attention on the HIV risk behaviors of cocaine abusers using data from the National Institute on Drug Abuse (NIDA) Cooperative Agreement for AIDS Community-Based Outreach/Intervention Research Program. The Cooperative Agreement consists of 23 sites, with 22 sites located in the US (including Puerto Rico) and one site in Brazil, and has included over 28,000 subjects recruited using street outreach. All Cooperative Agreement subjects were administered the NIDA risk behavior assessment (RBA) which provides detailed information about injection drug use behaviors, crack cocaine use and sexual behaviors. The RBA serves as the source of basic data for all papers in this issue which includes work describing local studies in St. Louis, North Carolina and Brazil as well as analysis of the National Database from researchers in Denver, Washington and Kentucky. In general, the studies focus on the etiology of HIV risk behaviors by empirically identifying the antecedents of individual HIV risk behaviors among cocaine users. These predictors of risk and protective behavior include the severity of crack cocaine, comorbid antisocial personality disorder and depression, alcohol consumption, and typologies of crack and injection drug use. Overall, the studies show that NIDA's prevention intervention is feasible and effective in many settings. The success of the studies which are included in this special issue is a testament to the feasibility of NIDA's science-based prevention interventions.