Although Kaposi sarcoma (KS) initially was described over a century ago, its biology remains enigmatic and conflicting. A recently discovered pathogen, KS-associated herpesvirus (KSHV) (also known as human herpesvirus 8 [HHV8]), is found in tissues from all four forms of KS: classic, iatrogenic, endemic (African), and HIV-associated. This universal detection of KSHV/HHV8 suggests a central role for the virus in the development of KS and a common etiology for all KS types. Whereas the classic type occurs mainly in older men of Mediterranean or Eastern European backgrounds and is not linked to impairment of the host immune response, iatrogenic and human immunodeficiencyvirus (HIV)-associated KS are linked to such conditions.