Kaposi’s sarcoma is the most common neoplasm observed in patients with AIDS. There is epidemiological and molecular evidence that infection with KSHV is predicted infectious cause of KS; moreover many cytokines and viruses, including HIV, are the cofactors required for the development of AIDS-KS. The clinical picture and course of AIDS-KS varies and is unpredictable, with different response to therapy. In this article authors describe the own clinical experiences in therapy of AIDS-KS, and the reasons of therapeutical failure.