Non-AIDS-defining cancers have recently gained more attention, and it appears that several of these cancers may be more common the the HAART era. By most accounts in the literature, the overall risk of non-AIDS-defining cancer in HIV-infected persons is 2 to 3 times that in the general population. In this article, we review the literature on 5 of the most common non-AIDS-defining cancers (Hodgkin disease, anal cancer, hepatocellular carcinoma, oral cancer, and lung cancer) in the pre- and post-HAART periods. It remains unclear whether earlier initiation (CD4+ cell count above 350/microL) of antiretroviral therapy may be beneficial in preventing non-AIDS-defining cancer. Further large-scale, randomized, prospective studies on this question are warranted.