This chapter summarizes what is known about how a single viral RNA molecule can be selectively amplified into thousands of RNA progeny in infected cells. It specifically provides the roles of viral proteins and RNA sequences in RNA replication, and describes the kinetics and products of RNA replication in infected cells. Next, it explains the sites and compositions of viral replication complexes (RCs) in infected cells. Then, the chapter discusses the models that have been proposed to explain how viral positive and negative RNA species are made by the viral RNA-dependent RNA polymerase. Finally, it describes the coupling between translation and replication processes in infected cells. Poliovirus is used as the prototype of an enterovirus because most of the research has been performed with poliovirus infected cell. To accomplish the unique task of RNA-dependent RNA polymerization in infected cells, enteroviruses encode several proteins required for viral RNA synthesis. Open questions about the mechanism of viral synthesis include the nature o f the RNA primers for positive- and negative-strand RNA synthesis, the source of specificity for the viral template RNA, and the relationship between translation and RNA synthesis, which may occur simultaneously in the infected host cell cytoplasm. Some of these questions may be studied with the recently discovered cellfree system.