Kaposi sarcoma (KS) is a complex cancer that arises from the initial infection of an appropriate endothelial or progenitorcell by Kaposi Sarcoma Herpesvirus/Human Herpesvirus-8 (KSHV/HHV8). However, the majority of KS cases occur wheninfected patients also suffer from some coincident form of immune deregulation, providing a favorable microenvironmentfor tumor development. Cellular hallmarks of KS progression include both the hyper-proliferation of KSHV-infectedcells and the infiltration of immune modulatory cells into KS lesions, which together result in chronic inflammation,the induction of angiogenesis and tumor growth. This review describes the current understanding of the interactionsbetween KSHV and host responses that result in this unusual cancer, along with existing treatments and prospects forfuture therapeutic approaches.