Fosamprenavir (Lexiva, GlaxoSmithKline/Vertex) is the latest protease inhibitor (PI) approved by FDA for the treatment HIV-1 infection. A prodrug of amprenavir (APV), fosamprenavir has improved solubility and bioavailability over the parent PI, allowing for once- or twice-daily dosing and a decreased pill size and burden. In clinical trials, fosamprenavir was studied alone or boosted with ritonavir (RTV) in both HIV treatment-naïve and -experienced patients. In both patient populations, fosamprenavir decreased HIV RNA, increased CD4 cell counts from baseline, and increased the proportion of patients reaching undetectable viral loads (<400 and <50 copies/mL). Patients who received treatment with fosamprenavir demonstrated protease gene mutations different than those commonly seen with other PIs (except APV). Fosamprenavir appears to have an adverse effect profile similar to that of other PIs.