An increased prevalence of insulin resistance, glucose intolerance and diabetes has been reported in HIV infection in the highly active antiretroviral therapy (HAART) era. This development might be clinically significant because of its association with cardiovascular morbidity and mortality as well as the therapeutic challenges of managing polypharmacy. The development of insulin resistance, glucose intolerance and diabetes could be related to the underlying HIV infection, the contribution of different antiretroviral agents, treatment-associated weight gain, immune restoration, as well as the non-HIV related factors. Dissecting these factors in clinical practice might be difficult. Clinical studies include short-term treatments in healthy, non-HIV-infected individuals; randomized, controlled trials; comparative studies of different HAART regimens; and randomized studies of switching regimens in patients with viral suppression and stable immune function. This article reviews the latest knowledge regarding the epidemiology, pathogenesis, prevention and treatment of insulin resistance, glucose intolerance and diabetes mellitus in HIV-infected individuals.