Injection drug use of psychotropic agents for nontherapeutic purposes is associated with some of the most pernicious infectious diseases seen in the United States. There is an inextricable link between infection, injection drug use (IDU) and other risk behaviors, especially those related to sexual activity. A number of national surveys now provide excellent databases to track the breadth, scope and impact of IDU across the United States. The prevalence of heroin use has increased over the past decade with larger numbers of users presenting for treatment of drug use disorders. A host of serious infections can result from IDU. Prevention and early intervention with evidence-based harm-reduction strategies are crucial to reducing and eliminating these odious consequences.