Fosamprenavir, the prodrug formulation of amprenavir, is a protease inhibitor recently approved in the US for the treatment of HIV infection. This agent combines the pharmacological profile of amprenavir with a low pill burden and flexible dosing schedule. Three large international trials have been completed. In treatment-naive patients, fosamprenavir, both ritonavir-boosted and -unboosted, met primary end points of non-inferiority against nelfinavir. Among naive patients, no protease inhibitor mutations emerged in those failing the boosted fosamprenavir regimen. Boosted fosamprenavir was compared to lopinavir/ritonavir in treatment-experienced patients. Non-inferiority was not achieved but similar numbers of patients achieved viral suppression when fosamprenavir was dosed twice-daily. Fosamprenavir demonstrates a favourable lipid profile in naive patients, and a low incidence of adverse effects. Fosamprenavir, as with lopinavir/ritonavir, distinguishes itself among other protease inhibitors with its potent activity in those with advanced HIV. Future trials comparing fosamprenavir with current standard regimens will further assist in defining its role in clinical practice.