Adhesion of cells to each other or to the extracellular matrix provides essential signals that regulate many cellular functions including cell migration, proliferation, differentiation and apoptosis. The integrin superfamily orchestrates many of these complex adhesive events through regulated interactions with a large variety of ligands. Crystallization of some ligands and of a ligand-binding integrin domain, reviewed here, together with extensive mutagenesis studies are beginning to shed light on the inner workings of these receptors.