Unraveling the mysteries associated with the etiology of KS is of tremendous public health significance. Whereas the introduction of prophylaxis has led to a decreased incidence of Pneumocystis carinii pneumonia, the incidence of KS has remained relatively stable and treatment of the HIV-infected KS patient remains a challenge. The last year has brought forth significant breakthroughs in KS research. Although KSHV has only recently been described, rapid progress is being made in understanding the role of this virus in the pathophysiology of the various forms of KS. It is too early to conclude whether KSHV is the elusive 'KS cofactor' or if all forms of KS share a common etiology, but it appears to be the single most plausible agent to be identified to date. Since all cancers are multifactorial in origin, it is likely that other host, environmental and possibly other viral cofactors could influence the risk of developing KS. The search for such cofactors must continue. Even if KSHV plays a central role, the exact mechanisms by which HIV and KSHV may interact to induce KS lesions, the tendency for KS to occur among homosexual men relative to other HIV transmission groups, and the reasons for the aggressive course of this neoplasm in HIV-infected persons remain to be determined. If a causal association can be established, KSHV could provide a model for the understanding of virus-induced neoplasia, like its cousin EBV. Although important questions regarding the specificity and temporality of KSHV and KS remain unanswered, the development and application of a sensitive serodiagnostic tool in longitudinal studies will be a crucial next step.