The essential event in picornavirus entry is the delivery of the RNA genome to the cytoplasm of a target cell, where replication occurs. In the past several years progress has been made in understanding the structural changes in the virion important for uncoating and RNA release. In addition, for several viruses the endocytic mechanisms responsible for internalization have been identified, as have the cellular sites at which uncoating occurs. It has become clear that entry is not a passive process, and that viruses initiate specific signals required for entry. And we have begun to recognize that for a given virus, there may be multiple routes of entry, depending on the particular target cell and the receptors available on that cell.