Injecting drug use is a major driver of HIV infections in Eastern Europe, the Commonwealth of Independent States, North Africa, the Middle East, and many parts of Asia and North America. We provide a global overview of the epidemiology of HIV infection among drug users and present current drug use trends that may constitute important epidemic drivers. We describe trends in ethnic disparities among injecting drug using (IDU) populations in the United States, and comment upon how these trends may now be changing. We present examples where HIV infection among non-IDUs who use cocaine, crack, and methamphetamine by other routes of administration is similar to that among IDUs, and discuss potential mechanisms of HIV spread in this overlooked population. Finally, we comment upon the potential implications of these observations for HIV interventions among IDU and non-IDU populations, taking into account different strategies that are needed in settings where HIV and/or injecting drug use has been established, or threatens to emerge.