Fosamprenavir is a recently licensed protease inhibitor (PI) for the treatment of patients with HIV. It has potent antiviral activity when boosted by ritonavir and produces durable virological suppression when combined with other antiretroviral drugs. In addition, it is well tolerated with a good safety profile, and can be taken once or twice daily with no food restrictions. Trough plasma levels obtained with once or twice daily boosted fosamprenavir are above the mean protein-binding adjusted IC50 values for wild-type and PI-resistant virus. When given twice daily boosted, no significant pharmacokinetic (PK) interaction is seen with tenofovir, the nucleoside reverse transcriptase inhibitors (NRTIs), efavirenz or nevirapine, and there is no requirement for any dose adjustment. Interactions with other PIs are difficult to predict. A reduction in plasma amprenavir level is seen when fosamprenavir or amprenavir is combined with ritonavir-boosted lopinavir, saquinavir or tipranavir: reductions in lopinavir and saquinavir plasma levels are also seen. Various dosing strategies have been evaluated to overcome these negative interactions. With unboosted atazanvir, an increase in amprenavir levels is found. This article will focus on the pharmacokinetics of ritonavir-boosted fosampreanvir and review drug interactions with other antiretroviral (ARV) and non-ARV agents.