Kaposi's sarcoma is a puzzling condition of unclear, possibly endothelial origin. It is divided into four distinct types regarding the affected population: classic in elder men of Ashkenazi Jewish and Mediterranean origin; endemic in African infants and young males; iatrogenic in patients under immunosuppressive regimens; epidemic in men having sex with men affected by AIDS. The exact etiopathogenesis of Kaposi's sarcoma continues to elude its researchers. Nonetheless, it has been discovered that human herpesvirus 8 is essential but not sufficient for sarcoma development. Also, iron exposure of populations inhabiting regions with volcanic soils has been suggested to play a pivotal role in the classic and endemic Kaposi's sarcoma etiology. The epidemic Kaposi's sarcoma is strongly associated with HIV's detrimental effect on immune system and HIV's Tat protein proangiogenic properties. Because Kaposi's sarcoma is found also in men having sex with men without AIDS, it has been proposed that certain lifestyle features (e.g. massive semen exposure and inhalant nitrites) may promote transformation of endothelial cells of both lymphatic and vascular origin. Despite numerous studies on Kaposi's sarcoma, it continues to be an incurable disease. The therapeutic approach includes local treatment and systemic administration of cytotoxic, immunomodulator and antiviral drugs. Because of the increasing prevalence of Kaposi's sarcoma, especially in certain parts of Africa, a better understanding of this condition is necessary.