Each of the 24 known integrin subunits has now been inactivated in mice, and a growing number of conditional null lines are becoming available. Lines of mice expressing null mutations in integrin subunit genes have taught us a great deal about the remarkably diverse functions that integrins perform in vivo in mammals. Thorough evaluation of the phenotypes manifested by these lines has also revealed a number of previously unexpected integrin ligands and signaling partners. In this article, we review approaches that can contribute to optimal use of this valuable resource.