Viruses attach to specific receptors, but identified receptors are often absent from the epithelial surfaces where infections begin. Viruses can bind to alternative receptor molecules present on epithelial surfaces and they can enter hosts in ways that bypass mucosal barriers to infection. To understand how viruses cross the mucosa to initiate infection we need new information about the mechanisms of attachment and entry into cells, but we also need in vivo studies to define precisely where infection occurs.