Virus entry is initiated by recognition by receptors present on the surface of host cells. Receptors can be major mediators of virus tropism, and in many cases receptor interactions occur in an apparently programmed series of events utilizing multiple receptors. After receptor interaction, both enveloped and nonenveloped viruses must deliver their genome across either the endosomal or plasma membrane for infection to proceed. Genome delivery occurs either by membrane fusion (in the case of enveloped viruses) or by pore formation or other means of permeabilizing the lipid bilayer (in the case of nonenveloped viruses). For those viruses that enter cells via endosomes, specific receptor interactions (and the signaling events that ensue) may control the particular route of endocytosis and/or the ultimate destination of the incoming virus particles. Our conception of virus entry is increasingly becoming more complex; however, the specificity involved in entry processes, once ascertained, may ultimately lead to the production of effective antiviral agents.