In the United States, drug users have dramatically reduced drug-related risk behaviors but continue sexual behaviors that place them at risk for human immunodeficiency virus (HIV) infection. Successful interventions are likely to be those that intervene at multiple levels, yet, historically, sexual interventions for drug users have primarily addressed only personal factors, such as condom use. Sexual risk arises from personal factors (e.g., perceived vulnerability and protective behaviors); interpersonal factors (e.g., relationship type and a partner's risk profile); social factors (e.g., gender roles and sexual mixing patterns among and between networks); and, finally, community-level factors (e.g., access to preventive methods and the prevalence of a sexually transmitted pathogen within a network). For female drug users, multiple sources of risk plus concurrent drug use during sex pose additional prevention challenges that disproportionately elevate their risk of sexually acquired HIV infection. New, multimodal interventions need to be developed and tested to more effectively address the many sources of sexual risk facing female drug users.