Kaposi's Sarcoma (KS) is a multicentric angioproliferative cancer of endothelial cells (ECs) caused by Human Herpesvirus 8 (HHV8) characterized by clinical heterogeneity depending on the host immune conditions. Despite its incidence has dramatically decreased in developed countries after the introduction of Highly Active Antiretroviral Therapy (HAART), KS remains the most frequent tumor in HIV-infected patients worldwide. Clinical presentation varies from an indolent slowly progressive behavior, generally limited to the skin, to an aggressive and rapidly progressing disease. In more than 50% of cases, the skin lesions are often associated with a more or less important visceral involvement, particularly to the oral cavity and the gastrointestinal tract that are involved in 35% and 40% of cases respectively. A large number of treatments can be used both as local and as systemic therapy. Particularly, HAART represents the first treatment in patients with moderate lesions limited to skin, and it can be sufficient to reduce significantly the size of lesions and, often, the complete disappear in 35% of cases after 3-9 months of treatment. In case of a rapidly progressive disease with extensive cutaneous and/or visceral involvement systemic drugs are used such as the liposomal anthracyclines pegylated liposomal doxorubicin (PLD) and daunorubicin citrate liposome (DNX), the combined treatment adriamycin-bleomycin-vincristine (ABV) and bleomycin-vincristine (BV), Paclitaxel and Interferon-alfa. In patients with limited skin localization, the local treatment can play an important role. Local medical therapy is based on the use of alitretinoin, antineoplastic drugs vincristine, vinblastine and bleomycin and Sodium Tetradecyl Sulfate (STS). In addition to medical therapy, physical treatment, such as cryotherapy and radiotherapy, are also commonly used.