HIV can spread rapidly between people who inject drugs (through injections and sexual transmission), and potentially the virus can pass to the wider community (by sexual transmission). Here, we summarise evidence on the effectiveness of individual-level approaches to prevention of HIV infection; review global and regional coverage of opioid substitution treatment, needle and syringe programmes, and antiretroviral treatment; model the effect of increased coverage and a combination of these three approaches on HIV transmission and prevalence in injecting drug users; and discuss evidence for structural-level interventions. Each intervention alone will achieve modest reductions in HIV transmission, and prevention of HIV transmission necessitates high-coverage and combined approaches. Social and structural changes are potentially beneficial components in a combined-intervention strategy, especially when scale-up is difficult or reductions in HIV transmission and injection risk are difficult to achieve. Although further evidence is needed on how to optimise combinations of interventions in different settings and epidemics, we know enough now about which actions are effective: the challenge is to deliver these well and to scale.