The epidemiology of AIDS-related Kaposi’s sarcoma (KS) predicted that a nonubiquitous sexually transmitted agent was central to its etiology. An assessment of Hill’s criteria for causality reveals there is now sufficient evidence to declare Kaposi’s sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8, a necessary, albeit not sufficient, cause of KS. The most compelling evidence comes from longitudinal studies presented in the past year that demonstrate that KSHV infection temporally precedes and is independently associated with AIDS-related KS even after adjustment for other potential etiologic factors. In the United States and Northern Europe, many studies have now shown that KSHV can be sexually transmitted among homosexual men, but determining specific routes of sexual transmission is methodologically challenging, and initial results are conflicting. Data are also emerging that demonstrate nonsexual modes of transmission. Spread via renal allograft appears to occur, and in endemic areas of Europe and Africa, nonsexual horizontal and perhaps vertical spread are the dominant modes of transmission.