Injecting use of heroin has been the highest risk substance use behavior for HIV since the beginning of the pandemic. These risks extend beyond individual levels to networks of drugs users and to wider social contexts that have been referred to collectively as the risk environment. Investigations of individual, network, and risk environment level associations with heroin availability, use, and subsequent spread among injecting drug users (IDUs) have been conducted in multiple settings, but much less is known about the world's center of illicit opium production and heroin exports-Afghanistan. Recent outbreaks of injecting drug use and of HIV infection attributed to IDUs in several African countries suggest that heroin use is expanding into new regions. This article explores the epidemiology of HIV among drug users in several risk environments, the epidemiology of heroin and its associations with HIV outbreaks among IDUs in Central Asia and the Commonwealth of Independent States, and the drug use and IDUs outbreaks now emerging in Africa. The dearth of targeted, evidence-and human rights-based responses to these epidemics is explored as a structural driver of HIV spread in these settings.