Polyomaviruses are small, tumorigenic, nonenveloped viruses that infect several different species. Interaction of these viruses with cell surface receptors represents the initial step during infection of host cells. This interaction can be a major determinant of viral host and tissue tropism. This chapter reviews what is currently known about the cellular receptors for each of five polyomavirus family members: Mouse polyomavirus (PyV), JC virus (JCV), BK virus (BKV), Lymphotropic papovavirus (LPV) and Simian virus 40 (SV40). These polyomaviruses serve to illustrate the enormous diversity of virus-cell surface interactions and allow us to closely evaluate the role of receptors in their life cycles. The contribution of other factors such as transcriptional regulators and signaling pathways are also summarized.