Infection with human immunodeficiency virus (HIV) results in inevitable progressive deterioration of the immune system in the majority of untreated patients. Prospects for virus eradication are remote, because HIV establishes long-lived reservoirs during the earliest stages of infection that are impervious to available antiviral therapies. Understanding how the immune system copes with this illness and other chronic viral infections is the key to designing future strategies for long-term control of viremia. Valuable insights have been gained from 2 populations in particular: patients with chronic, long-term, nonprogressing infections, in whom viremia is controllable in the absence of antiviral medications, and acutely infected patients, in whom the initial HIV-specific immune response might be preserved and augmented by timely intervention. These cases of immune control of HIV provide hope for the development of improved vaccine products that may eventually produce vaccine-induced immunity that will enhance durable control of HIV infection.