Specific antagonists have been successfully developed for several different integrins. Clinical trials have been initiated to study therapeutic uses of these inhibitors in cancer, thrombosis, and inflammatory diseases. Most efforts to date have focused on the platelet integrin αIIbβ3, endothelial αvβ3, and the leukocyte integrin α4β1. However, the integrin family contains additional members with interesting tissue specificities and functional properties that could also be useful molecular targets for disease intervention. In many cases, specific recognition motifs for these integrins have not been identified, which has precluded development of specific antagonists. Our recent studies of thrombospondin-1 and thrombospondin-2 recognition by integrins have revealed novel motifs for a3b1 and a6b1 integrins as well as new motifs recognized by the well studied α4β1 integrin. These three integrins play distinct roles in angiogenesis and its modulation by thrombospondins. This review will discuss recent insights into the specificities of α3β1 and α6β1 integrins, their functions in angiogenesis, and potential applications for antagonists of these integrins and of α4β1 to control pathological angiogenesis and other diseases.