PURPOSE OF REVIEW: The social networks of people who inject drugs (PWID) have long been studied to understand disease transmission dynamics and social influences on risky practices. We illustrate how PWID can be active agents promoting HIV, HCV, and overdose prevention. RECENT FINDINGS: We assessed drug users' connections and interactions with others at risk for HIV/HCV in three cities: New York City (NYC), USA (n = 539); Pereira, Colombia (n = 50); and St. Petersburg, Russia (n = 49). In all three cities, the majority of participants' network members were of a similar age as themselves, yet connections across age groups were also present. In NYC, knowing any opioid user(s) older than 29 was associated with testing HCV-positive. In NYC and St. Petersburg, a large proportion of PWID engaged in intravention activities to support safer injection and overdose prevention; in Pereira, PWID injected, had sex, and interacted with other key groups at risk. People who use drugs can be active players in HIV/HCV and overdose risk- reduction; their networks provide them with ample opportunities to disseminate harm reduction knowledge, strategies, and norms to others at risk. Local communities could augment prevention programming by empowering drug users to be allies in the fight against HIV and facilitating their pre-existing health-protective actions.