Prevention of heterosexual transmission of HIV between and from drug users is important for controlling the local and global HIV heterosexual epidemic. Sex risk reduction interventions and health-related interventions are important for reducing the sex risk behaviors of drug users. Sex risk reduction interventions address individual-level, peer-level, and structural-level determinants of risk reduction. Health-related interventions include HIV counseling and testing, prevention and treatment of sexually transmitted diseases, and delivery of highly active antiretroviral therapy. It is important to adapt effective interventions implemented in resource-rich countries to the realities of the resource-constrained settings and to address relevant contextual factors.