Current recommendations state that antiretroviral therapy (ART) should be commenced before the onset of severe HIV-associated immune deficiency and the development of AIDS-defining infections or malignancies. However, many patients only present and are diagnosed with HIV infection when they already have advanced disease. The optimal treatment for patients with advanced HIV disease remains to be defined. Key management questions include whether the virological and immunological responses to ART are comparable to those seen in patients with less advanced disease; whether the efficacy of different antiretroviral (ARV) regimens differs in patients with advanced disease; and whether there is an increased risk of drug toxicity and the immune reconstitution inflammatory syndrome.