Antiretroviral management of treatment-naive patients begins with the decision of when to start treatment. Current treatment guidelines suggest starting therapy in anyone with AIDS, HIV-related symptoms, or a CD4 cell count less than 200/mm3 regardless of symptoms. Starting treatment in asymptomatic patients with CD4 of more than 200 requires consideration of a number of pros and cons, and individualization is the key. Recommended first-line antiretroviral regimens consist of two nucleoside reverse transcriptase inhibitors together with either a nonnucleoside reverse transcriptase inhibitor or a protease inhibitor (with or without ritonavir boosting). The goal of antiretroviral therapy is maximally to suppress viremia, enhance or improve immune function, and prevent clinical progression.