Integrins are a structurally elaborate family of adhesion molecules that transmit signals bi-directionally across the plasma membrane by undergoing large-scale structural rearrangements. By regulating cell-cell and cell-matrix contacts, integrins participate in a wide range of biological processes, including development, tissue repair, angiogenesis, inflammation and haemostasis. From a therapeutic standpoint, integrins are probably the most important class of cell-adhesion receptors. Recent progress in the development of integrin antagonists has resulted in their clinical application and has shed new light on integrin biology. On the basis of their mechanism of action, small-molecule integrin antagonists fall into three different classes. Each of these classes affect the equilibria that relate integrin conformational states, but in different ways.