Kaposi's sarcoma (KS) is a mesenchymal tumour involving blood and lymphatic vessels. Only recently has the pathogenesis of this extraordinary neoplasm been elucidated. Viral oncogenesis and cytokine-induced growth together with some state of immunocompromise represent important conditions for this tumour to develop. In 1994, a novel virus was discovered and termed human herpesvirus 8 (HHV8), also known as Kaposi's sarcoma-associated herpes virus, which can be found in all types of KS, whether related to HIV or not. In the era of highly active antiretroviral therapy (HAART), the incidence of AIDS-KS has considerably declined, probably due to enhanced immune reconstitution and anti-HHV8-specific immune responses. If HAART is able to prevent spreading of KS, local therapy of KS may become an essential component of patient management. Part 1 of the review covers the epidemiology, environmental predispositions, clinical manifestations, and therapy of KS. Newer treatments such as pegylated liposomal anthracyclines and experimental strategies are discussed. We also present rationales and graduated treatment algorithms for local and systemic therapy in patients with KS to appropriately meet the challenges of this extraordinary neoplasm. Part 2, to be published next month, will summarise recent insights in the pathogenesis of KS and will discuss other HHV8-related diseases such as Castleman's disease and primary effusion lymphoma.