Despite the effectiveness of existing HIV prevention strategies for people who inject drugs (PWID), uncontrolled outbreaks of HIV among this group are common and occur around the world. In this Review, we summarise recent evidence for novel and established HIV prevention approaches to eliminate HIV transmission among PWID. Effective HIV prevention strategies include mobile needle and syringe programmes, pre-exposure prophylaxis, supervised injection facilities, and, to a lesser extent, some behavioural interventions. Studies have also shown the cost-effectiveness of long-standing HIV prevention strategies including needle and syringe programmes, opioid agonist therapy, and antiretroviral therapy for prevention. Although each individual intervention can reduce the risk of HIV acquisition among PWID, there is a consensus that a combination of approaches is required to achieve substantial and durable reductions in HIV transmission. Unfortunately, in many settings, the implementation of these interventions is often limited by public and political opposition that manifests as structural barriers to HIV prevention, such as the criminalisation of drug use. Given that there is ample evidence showing the effectiveness of several HIV prevention methods, social and political advocacy will be needed to overcome these barriers and integrate innovative HIV prevention approaches with addiction science to create effective drug policies.