This paper discusses the user side of harm reduction, focusing to some extent on the early responses to the HIV/AIDS epidemic in each of four sets of localities-New York City, Rotterdam, Buenos Aires, and sites in Central Asia. Using available qualitative and quantitative information, we present a series of vignettes about user activities in four different localities in behalf of reducing drug-related harm. Some of these activities have been micro-social (small group) activities; others have been conducted by formal organizations of users that the users organized at their own initiative. In spite of the limitations of the methodology, the data suggest that users' activities have helped limit HIV spread. These activities are shaped by broader social contexts, such as the extent to which drug scenes are integrated with broader social networks and the way the political and economic systems impinge on drug users' lives. Drug users are active agents in their own individual and collective behalf, and in helping to protect wider communities. Harm reduction activities and research should take note of and draw upon both the micro-social and formal organizations of users. Finally, both researchers and policy makers should help develop ways to enable and support both micro-social and formally organized action by users.