Integrins are cell adhesion receptors that have many important roles in organ development and tissue integrity, functioning to mediate interactions between cells and the ECM. The entire repertoire of integrins is vast, and the specific roles of each are determined by unique integrin-ligand interactions. These interactions allow for dynamic regulation of multiple processes. Despite intense efforts to elucidate individual integrin ligands, existing methods have been limiting. In this chapter, we describe methods developed in our laboratory to identify new integrin ligands that should be useful for characterizing novel integrin functions. These methods are applicable for studies on a variety of integrins, and may be extended to other cell surface receptors as well.