The toxicity of antiretroviral therapy is an increasingly important issue in the management of patients with human immunodeficiency virus (HIV). With sustained major declines in opportunistic complications, HIV infection is increasingly a more chronic disease, and so more drugs are being used in more patients for longer periods. However, permanent and near-perfect adherence to antretroviral therapy is needed to maximize its long-term benefits. Although adverse reactions to antiretroviral therapy are common, and profoundly affect its clinical efficacy by limiting adherence, many such reactions are poorly studied and analysed, and are under-reported. This article summarizes adverse events associated with antiretroviral therapy, and discusses weaknesses and possible solutions in the study, analysis and reporting of adverse events that could improve antiretroviral drug development.