Injecting drug use is driving HIV epidemics in many countries around the world. There is evidence that such epidemics can be averted, halted and reversed if comprehensive HIV programmes targeting drug users are put into place. The term ‘harm reduction’ is used widely to describe the goals, policies and interventions of such programmes. However, despite its rapidly expanding use, the term has no universally accepted definition. This paper aims to describe the evolution and branding of the term ‘harm reduction’ and the adoption of the concept across a wide range of countries. It highlights a range of issues that remain controversial in the harm reduction discourse related to HIV and injecting drug use, including: the definition of ‘harm reduction’ and related terms; the scope of harm reduction; the promotion of a public health versus drug control dichotomy; the feasibility and appropriateness of harm reduction in low- and middle-income countries; and the strength of evidence on harm reduction interventions. The paper argues that harm reduction should be a core element of a public health response to HIV/AIDS where injecting drug use exists. The effectiveness of policies and programmes targeting drug users should be measured against public health outcomes. This requires the alignment of drug control measures with public health goals. A ‘model package’ for harm reduction is proposed, which provides guidance to countries on the selection of evidence-based policies and interventions, including: interventions for reducing HIV transmission; treatment of HIV/AIDS and associated comorbidities; appropriate models of service delivery; creation of supportive policy, legal and social environments; and strengthening of strategic information systems to better guide responses.