Kaposi’s Sarcoma (KS) is an angiogenic tumor involving skin, mucosa and splanchnic organs. It is caused by Human Herpes Virus 8 (HHV8), when in the presence of other cofactors, such as an immune dysregulation. KS is particularly frequent in HIV-infected individuals. The major goals of treatment are to prevent disease progression, to reduce tumor and edema, to avoid organ compromise, and to relieve psychological stress. The importance and the high cancer risk offered by this co-infection, together with the spread of both these viruses, and the fact that angiogenesis is such an important characteristic of KS led to a lively interest in finding a definitive therapy. Most of the ongoing studies are focused on finding an application of old drugs in KS. Unfortunately, given the number of studies with different targets, it seems we are still far from completely understanding this disease and obtaining a “cure” which could be effective and safe for everyone. Further studies will hopefully offer new and definitive solutions.