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HIV prevention among drug users continues to be a daunting challenge. Previous efforts have shown limited success. A major research question for the next generation of HIV prevention interventions for drug users is how do we design, implement, and evaluate harm reduction interventions that reach the appropriate audiences, are programmatically sustainable, maintain behavior change, and lead to meaningful changes in participants' lives. The goal of this chapter is to critique the current state of HIV prevention research and to propose using additional social science theories and methods in future approaches to behavior change. The first section of this chapter examines some of the historical and psychological factors that may have hindered progress in the field of behavioral HIV prevention. The next section presents a theoretical foundation for a social influence approach to HIV prevention interventions for drug users that considers opportunity structures within an individual's social environment. This approach emphasizes behavioral Settings, Norms, and Network Approaches to AIDS Prevention (SNNAAP). By capitalizing on naturally occurring social influence processes, promoting HIV-related behavior change among drug users may be possible. The section discusses social behavioral theories, social-oriented research methods, and individual-level factors that have been inadequately pursued in the field of HIV prevention. Examples of interventions that have incorporated social behavioral theory are presented. Next, several approaches to improving HIV prevention research methods are discussed. Finally, future directions of HIV prevention research are proposed.