Merkel cell polyomavirus (MCPyV) is the most recently discovered human oncogenic virus. MCPyV asymptomatically infects most of the human population. In the elderly and immunocompromised, however, it can cause a highly lethal form of human skin cancer called Merkel cell carcinoma (MCC). Distinct from the productive MCPyV infection that replicates the viral genome as episomes, MCC tumors contain replication-incompetent, integrated viral genomes. Mutant MCPyV tumor antigen genes expressed from the integrated viral genomes are essential for driving the oncogenic development of MCPyV-associated MCC. In this chapter, we summarize recent discoveries on MCPyV virology, mechanisms of MCPyV-mediated oncogenesis, and the current therapeutic strategies for MCPyV-associated MCCs.