Since the emergence of the HIV pandemic in the 1980s, there have been great advances in the treatment of HIV through potent and effective antiretroviral therapy. This has led to HIV-infected individuals presenting with fewer opportunistic infections and, subsequently, leading longer lives in better health. Nevertheless, there are HIV-positive people in both high- and low-resource settings who may present late with marked immunodeficiency or have no access to adequate medical care and antiretroviral therapy. Within these populations, opportunistic infection rates still remain unacceptably high. This article outlines the varie;ty of opportunistic infections that can be seen in clinical practice, and highlights the way in which these infections can be pre-empted, diagnosed and treated according to best practice guidelines.