Atazanavir (ATV) is an HIV protease inhibitor (PI) that was approved as antiretroviral agent in year 2003. Ritonavir (RTV) enhances ATV plasma exposure and increases its barrier to resistance. Antiretroviral therapy with ATV plus RTV (ATV/r) has demonstrated high potency for achieving virological suppression in antiretroviral-na ve patients and in simplification strategies. In rescue interventions, ATV/r-based combinations have shown to be equivalent in terms of viral response to other PI/r-containing regimens. In contrast with all other PIs, ATV has also demonstrated efficacy when given unboosted with RTV, an option attractive in special situations. Other benefits of the drug are its good metabolic and gastrointestinal profile. Its main adverse event is hyperbilirubinemia, since ATV inhibits the hepatic uridin-glucoronyl-transferase. A signature mutation at the protease gene, I50L, confers loss of susceptibility to the drug whereas it may confer hypersusceptibility to other PIs. Many ATV studies have provided data until or beyond week 96, supporting the efficacy and safety of the drug in the long-term.