The virus particles described in the previous chapters of this book are vehicles that transmit the viral genome and the infection from cell to cell. To initiate the infective cycle, the viral genome must therefore translocate from the viral particle to the cell cytoplasm. Via distinct proteins or motifs in their outermost shell, the particles of animal viruses or bacteriophages attach initially to specific receptors on the host cell surface. These viral receptors thus mediate penetration of the viral genome inside the cell, where the intracellular infective cycle starts. The presence of these receptors on the cell surface is a principal determinant of virus-host tropism. Viruses can use diverse types of molecules to attach to and enter into cells. In addition, virus-receptor recognition can evolve over the course of an infection, and viral variants with distinct receptor-binding specificities and tropism can appear. The identification of viral receptors and the characterization of virus-receptor interactions have been major research goals in virology. In this chapter, we will describe, from a structural perspective, several virus-receptor interactions and the active role of receptor molecules in virus cell entry.