The study of acute-transforming retroviruses and their oncogenes and of the multiple mechanisms deployed by DNA viruses to circumvent the growth-suppressive and proapoptotic function of tumor suppressor genes has provided the foundation of our current understanding of cancer biology. Unlike acute-transforming animal viruses, however, human tumor-associated viruses lead to malignancies with a prolonged latency and in conjunction with other environmental and host-related cooperating events. The relevance of viral infection to human cancer development has often been debated. We now know that at least six human viruses, Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HCV), human papilloma virus (HPV), human T-cell lymphotropic virus (HTLV-1) and Kaposi's associated sarcoma virus (KSHV) contribute to 10-15% of the cancers worldwide. Hence, the opportunity exists to fight cancer at the global scale by preventing the spread of these viruses, by the development and distribution of effective and safe antiviral vaccines, and by identifying their oncogenic mechanism. Here, we discuss the molecular events underlying the neoplastic potential of the human tumor-associated viruses, with emphasis on the enigmatic KSHV and its numerous virally hijacked proangiogenic, immune-evasive and tumor-promoting genes. The emerging information may facilitate the development of new molecular-targeted approaches to prevent and treat virally associated human malignancies.