Amprenavir (APV, Agenerase) is the fifth protease inhibitor (PI) available for clinical use. It is highly active and its pharmacokinetics allow convenient twice-daily administration. It is metabolised by the cytochrome P450 system, leading to a number of drug interactions that have been well defined. Mutations at codons 50 (along with additional changes at codons 46 and 47) lead to the development of resistance, both in vitro and in vivo. In over 200 drug-naive patients, APV-based combination therapy has led to maximal suppression of plasma viral load (generally below 50 copies/ml) in over 50% patients participating in clinical trials lasting 24 - 48 weeks. Benefit has also been demonstrated in over 500 previously treated patients, especially if they are naive to PIs as a therapy. APV-based therapy also appears to be effective in children. Major adverse effects observed in clinical usage have been gastrointestinal (GI) intolerance, skin rash and peri-oral paresthesias. At the present time, it is unclear whether APV offers any advantage over similar types of drugs. Overall, it may be easier to take than some other PIs, but the cost in terms of pill burden is quite high. The toxicity profile (especially the risk of serious skin rashes) may also be an issue. It may be also important in the treatment of isolates that are resistant to other PIs. Its specific role in therapy can only be clarified once the results of ongoing trials (particularly comparative trials of its use in previously treated patients) are available.