In recent years, our understanding of the molecular interaction of collagens with their cognate integrin receptors has remarkably improved. Structural elucidations of both the integrin and the collagenous triple helix have contributed to this achievement. The structures of an entire integrin ectodomain and of an A-domain, which is unique to the integrin α subunits of collagen-binding and leukocyte integrins, have been resolved crystallographically. Furthermore, a complex of such an integrin α subunit A-domain with its collagenous binding partner has revealed their interaction on the molecular level and gave first evidence in the conformational alterations which may convey the signal of ligand occupancy through the integrin into the cells. In parallel, the tissue distribution and biological functions of collagen-binding integrins have been characterised. Nowadays, the contribution of distinct integrins to different physiological and pathological processes is known. Among the best studied examples is the collagen-induced platelet activation and aggregation, in which α2β1 integrin is involved. Together with α1β1 integrin, it also plays a role in inflammatory processes. To manipulate processes which are mediated by collagen-binding integrins, compounds are developed which mimic the collagen ligand. Not only the structural information of the integrin:collagen-interaction but also improvements in the chemical synthesis of a collagenous triple helix facilitate the development of agonists and antagonists of collagen-binding integrins. Furthermore, another impact in this search comes from the discovery of high-affinity inhibitors from venoms, which lack a collagenous triple-helix.