During the potent antiretroviral therapy era, the incidence of AIDS-defining cancers has decreased and the incidence of non--AIDS-defining cancers (NADCs) has increased, as has the proportion of mortality associated with NADC in HIV-infected patients. The increase in NADCs is partly associated with increased longevity of the HIV-infected population, but it may also reflect consequences of increased immune activation and decreased immune surveillance as well as direct effects of HIV. The NADCs appear to have earlier onset and worse prognosis in HIV-infected patients than in the general cancer population. Among cancers that have increased in incidence are lung cancer, with its strong association with tobacco use, and skin cancers. Much remains to be learned about risk, risk reduction, optimal treatment, and drug interactions in HIV-infected cancer patients. This article summarizes a presentation on malignancies in HIV infection made by Ronald T. Mitsuyasu, MD, at an International AIDS Society-USA Continuing Medical Education course in San Francisco in May 2008. The original presentation is available as a Webcast at www.iasusa.org.