HIV-1 infection usually results in high level of viral replication leading to a progressive decline of CD4+ T cells and eventually to full blown AIDS. Long term non-progressors (LTNPs) are patients who have stable CD4 counts for more than 5 years without antiretroviral therapy. Most of these patients have detectable levels of viremia and eventually will progress to AIDS. Elite controllers or suppressors (ES) represent a distinct subset of untreated patients who appear to be able to completely control viral replication. These patients maintain viral loads below the limit of detection of commercial assays for many years and generally do not show any clinical signs of disease progression. The mechanisms responsible for this remarkable control may lead to the design of effective HIV-1 vaccines.