Aims Adherence to highly active antiretroviral therapy (HAART) is a key predictor of survival for human immunodeficiency virus (HIV)-infected people. Suboptimal adherence among marginalized populations such as HIV-positive drug users could be associated with clinical failure and the emergence of viral resistance. Objective To conduct a systematic review of studies assessing adherence to HAART among HIV-positive drug users (DU) and identify factors associated with non-adherence to HIV treatment. Data sources Seven electronic databases were searched for peerreviewed papers published in English, French, Spanish or Portuguese, from 1996 to 2007. Study selection and data abstraction Studies were excluded if they presented only qualitative data, were reviews themselves or assessed other populations without disaggregating data on DU. Findings on adherence were extracted and summarized. Data synthesis Forty-one studies were considered, which studied a total of 15 194 patients, the majority of whom were HIV-positive DU (n = 11 628, 76.5%). Twenty-two studies assessed adherence using patient self-reports, eight used pharmacy records, three used electronic monitoring [i.e. Medication Event Monitoring Systems (MEMS) caps], six studies used a combination of patient self-report, clinical data and MEMS-caps, and two analyzed secondary data. Overall, active substance use was associated with poor adherence, as well as depression and low social support. Higher adherence was found in patents receiving care in structured settings (e.g. directly observed therapy) and/or drug addiction treatment (especially substitution therapy). Conclusion While lower than other populations—especially among users of stimulants, incarcerated DU and patients with psychiatric comorbidities—adherence to HAART among HIV-positive DU can be achieved. Better adherence was identified among those engaged in comprehensive services providing HIV and addiction treatment with psychosocial support.