Recent advances in the understanding of HIV pathogenesis, the development of a new potent class of antiretroviral agents, and new data on the effectiveness of older, less potent agents when used in combination are resulting in a new era of more effective therapies for HIV. Three classes of antiretroviral agents are approved for clinical use: nucleoside and nonnucleoside RT inhibitors and protease inhibitors. These classes of drugs are limited in duration of effectiveness owing to the emergence of resistance. Problems with the potency of therapy and resistance can be overcome to some extent by using these agents in combination. The most promising regimen to emerge thus far appears to be the combination of zidovudine, lamuvidine, and a potent protease inhibitor such as indinavir. Multiple additional combination regimens are now in clinical trials, and data on other promising regimens with potent antiretroviral activity may soon appear. Short-term results obtained with such combination regimens are impressive and represent a considerable advance over older approaches to the treatment of HIV infection. Data on the long-term clinical and virologic effectiveness of new combination regimens are needed, however, before the true impact of these treatments on the prognosis for HIV-infected patients can be assessed.