Effective combination therapy for HIV/AIDS is now available and has made a major impact on HIV-related mortality and morbidity. The effects of even the most active of antiretroviral drugs are hampered by drug resistance and tolerability issues. Darunavir (TMC114), coadministered with low-dose ritonavir (darunavir/r), is a new HIV-1 protease inhibitor that has been designed to be active against both wild-type and multi-resistant virus. Darunavir/r 600/100 mg b.i.d. in a combination antiretroviral regimen in the POWER trials has provided treatment-experienced patients with substantially greater virological and immunological benefits compared with standard of care. This article reviews the presently available data on darunavir, its pharmacology, pharmacokinetics, drug-drug interactions and clinical trial results, as well as examining darunavir from a health economic perspective.