Polyomaviruses, as their name indicates, are viruses capable of inducing a variety of tumors in vivo. Members of this family, including the human JC and BK viruses (JCV, BKV), and the better characterized mouse polyomavirus and simian virus 40 (SV40), are small DNA viruses that commandeer a cell's molecular machinery to reproduce themselves. Studies of these virus-host interactions have greatly enhanced our understanding of a wide range of phenomena from cellular processes (e.g., DNA replication and transcription) to viral oncogenesis. The current chapter will focus upon the five known JCV early proteins and the contributions each makes to the oncogenic process (transformation) when expressed in cultured cells. Where appropriate, gaps in our understanding of JCV protein function will be supplanted with information obtained from the study of SV40 and BKV.