Integrin α1β1 is widely expressed in mesenchyme and the immune system, as well as a minority of epithelial tissues. Signaling through α1 contributes to the regulation of extracellular matrix composition, in addition to supplying in some tissues a proliferative and survival signal that appears to be unique among the collagen binding integrins. α1 provides a tissue retention function for cells of the immune system including monocytes and T cells, where it also contributes to their long-term survival, providing for peripheral T cell memory, and contributing to diseases of autoimmunity. The viability of α1 null mice, as well as the generation of therapeutic monoclonal antibodies against this molecule, have enabled studies of the role of α1 in a wide range of pathophysiological circumstances. The immune functions of α1 make it a rational therapeutic target.