Many early studies of injecting drug users (IDUs) suggested that most HIV infections in this population were due to needle sharing and that sexual transmission was negligible or was overshadowed by parenteral routes. A few of the early studies suggested a potentially important role for heterosexual transmission, but these tended to be limited to cross-sectional data or had only a few years of prospective follow-up. Studies of sexual risk factors for HIV infection among non-injecting drug users (NIDUs) are similarly sparse. Recently, investigators prospectively examined both drug-related and sexual risk factors for HIV seroconversion among male and female IDUs with an adequate number of person-years to identify statistically significant associations. Other studies among never and former IDUs have identified associations suggesting that sexual transmission accounts for a substantial number of HIV seroconversions in these populations. Herein, highlights are discussed from recent investigations among IDUs in Baltimore, Maryland, and corroborating findings from the literature. Results from a 10-year prospective analysis of the ALIVE study and an analysis of the REACH studies spanning a 7-year period indicate that sexual risk factors for HIV infection are important in both female and male IDUs. These findings underscore the need for HIV interventions among drug users that incorporate sexual risk reduction. Based on the existing literature, a narrow focus on injection-related risks is an ineffective prevention strategy. Interventions that target specific subgroups of high-risk IDUs, such as men who have sex with men and inject drugs (MSM-IDUs), sex worker-IDUs and HIV-infected IDUs, deserve special attention.