The incidence of AIDS-defining opportunistic infections has decreased markedly in persons with HIV who receive combination antiretroviral therapy, but less is known regarding the incidence of cancer. It does appear that the incidence of Kaposi sarcoma in persons receiving combination therapy has fallen dramatically. In contrast, reduction in the incidence of non-Hodgkin lymphoma (NHL) has been smaller. Based on few data, it appears that the incidence of primary CNS NHL is significantly decreasing, whereas the incidence of systemic NHL has changed little. Certain other cancers, comprising cervical cancer, Hodgkin disease, anal cancer, and conjunctival cancer, occur at increased rates in some populations with AIDS, but there are few data on incidence trends since the widespread use of combination therapy. In the future, cancers associated with long-term mild immune suppression and B-cell stimulation may occur at increased rates in long-term survivors of HIV infection.