AIDS-related Kaposi's sarcoma (KS) represents a complex interaction of host and viral factors. There are a number of fundamental questions surrounding the interplay between the disparate factors that can contribute to the pathogenesis and pathophysiology of this disease. Targets such as the enhancement of immune function, inhibition of angiogenic factors or immunostimulatory cytokines, inhibition of viral proteins such as Tat, or hormonal manipulations are now or will in the future become the focus of research to develop innovative anti-KS therapy and prevention measures. Antiviral approaches aimed at HIV or other viruses may potentially target a number of steps in KS pathogenesis. This article reviews diverse modalities--cytotoxic, antiviral, gene-directed, growth factor-targeted, and antiangiogenesis--that singly, or more likely in combination, stand to make an impact on the cure and prevention of AIDS-related KS.