Effective treatment regimens for HIV infection demand very high levels of adherence and people infected with HIV are expected to adhere to safer sex and drug use practices throughout their lives. Treatment nonadherence overlaps with continued unsafe sexual practices for some people living with HIV/AIDS. The co-occurrence of nonadherence and HIV transmission risk behavior poses particular risk for the spread of drug-resistant variants of HIV. There are common correlates of both nonadherence and risk behavior, particularly substance use and depression. Interventions designed to address treatment nonadherence and those designed to reduce risk behavior also share common elements, particularly self-efficacy enhancement and behavioral skills training. The common correlates and shared intervention elements suggest that integrated intervention approaches that simultaneously address adherence and risk reduction may be feasible. Research is currently testing interventions that simultaneously increase HIV treatment adherence and reduce behaviors that risk HIV transmission.