Tumor viruses have provided relatively simple genetic systems, which can be manipulated for understanding the molecular mechanisms of the cellular transformation process. A growing body of information in the tumor virology field provides several prospects for rationally targeted therapies. However, further research is needed to better understand the multiple mechanisms utilized by these viruses in cancer progression in order to develop therapeutic strategies. Initially viruses were believed to be associated with cancers as causative agents only in animals. It was almost half a century before the first human tumor virus, Epstein-Barr virus (EBV), was identified in 1964. Subsequently, several human tumor viruses have been identified including Kaposi sarcoma associated herpesvirus (KSHV), human Papillomaviruses (HPV), Hepatitis B virus (HBV), Hepatitis C virus (HCV), Human T lymphotropic virus (HTLV-1) and recently identified Merkel cell Polyomavirus (MCPyV). Tumor viruses are sub-categorized as either DNA viruses, which include EBV, KSHV, HPV, HBV, and MCPyV, or RNA viruses such as HCV and HTLV-1. Tumor-viruses induce oncogenesis through manipulating an array of different cellular pathways. These viruses initiate a series of cellular events, which lead to immortalization and proliferation of the infected cells by disrupting the mitotic checkpoint upon infection of the host cell. This is often accomplished by functional inhibition or proteasomal degradation of many tumor suppressor proteins by virally encoded gene products. The virally infected cells can either be eliminated via cell-mediated apoptosis or persist in a state of chronic infection. Importantly, the chronic persistence of infection by tumor viruses can lead to oncogenesis. This review discusses the major human tumor associated viruses and their ability to modulate numerous cell signaling pathways, which can be targeted for potential therapeutic approaches.