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The entry process of herpesviruses into host cells is complex and highly variable. It involves a sequence of well-orchestrated events that begin with virus attachment to glycan-containing proteinaceous structures on the cell surface. This initial contact tethers virus particles to the cell surface and results in a cascade of molecular interactions, including the tight interaction of viral envelope glycoproteins to specific cell receptors. These interactions trigger intracellular signaling and finally virus penetration after fusion of the viral envelope with cellular membranes. Based on the engaged cellular receptors and co-receptors, and the subsequent signaling cascades, the entry pathway will be decided on the spot. A number of viral glycoproteins and many cellular receptors and molecules have been identified as players in one or several of these events during virus entry. This chapter will review viral glycoproteins, cellular receptors and signaling cascades associated with the very first interactions of herpesviruses with their target cells.