We evaluated longitudinal rates of Kaposi's sarcoma and trends in CD4 cell counts at the time of Kaposi's sarcoma diagnosis during the HIV epidemic (1985-2008). Although rates of Kaposi's sarcoma have decreased, cases are now occurring at higher CD4 cell counts over time, with more than one-third of cases diagnosed in 2002-2008 occurring at CD4 cell counts of at least 350 cells/μl. These data support future studies evaluating the impact of highly active antiretroviral therapy initiation at higher CD4 cell counts to further reduce Kaposi's sarcoma.