Major advances in understanding the pathogenesis and treatment of human immunodeficiency virus (HIV) infection have been made recently. The reverse transcriptase and protease enzymes of HIV are currently the targets of antiretroviral therapy. Nucleoside analogues were the first class of antiretroviral drugs which demonstrated antiviral activity in treating patients. More recently protease inhibitors have provided new approaches in the treatment of HIV infection, with encouraging trial results in patients receiving combined therapy. This review presents their mechanisms of activity and patterns of resistance. Apart from these main drug groups many new compounds are under development.