Replication of the picornavirus genome is catalysed by a viral encoded RNA-dependent RNA polymerase, termed 3D polymerase. Together with other viral and host proteins, this enzyme performs its functions in the cytoplasm of host cells. The crystal structure of 3D polymerase from a number of picornaviruses has been determined. This review discusses the structure and function of the poliovirus 3D polymerase. The high error rates of 3D polymerase result in high sequence diversity such that virus populations exist as quasispecies. This phenomenon is thought to facilitate survival of the virus population in complex environments.