The second wave of the HIV epidemic, which increasingly affects injection drug users, women, and minorities, necessitates the development of primary care HIV services so that these individuals may benefit from new therapies. The ability to dramatically decrease vertical transmission of HIV from mother to child with antiretroviral therapy is encouraging. Better understanding of HIV pathogenesis, disease progression, antiviral therapy, and opportunistic infection prophylaxis are leading to more effective therapy and prevention. Clinical trials are ongoing to assess the efficacy of protease inhibitors in combination with nucleoside analog antiretroviral therapy to provide long term viral suppression and alter the natural history of HIV. Prophylaxis of pneumocystis, toxoplasma, MAC, TB, and invasive fungal infections is cost effective and leads to improved quality of life.