Integrins participate in many aspects of immunologic and inflammatory responses, especially those involving cell migration, adherence, and activation. Although leukocyte integrins such as complement receptor type 3 (CR3) are known to carry out certain functions without the intervention of other plasma membrane receptors, many plasma membrane proteins are now known to physically interact and functionally cooperate with integrins. Several of these interactions are highly dynamic within cell membranes; thus integrin-partner protein interactions change during certain physiological processes. This allows an extraordinary adaptability of the system to prime and promote proinflammatory signaling. Since our discovery of the CR3-FcgammaRIIIB interaction, the plasma membrane protein repertoire of beta1, beta2, and beta3 integrins has grown to include: FcgammaRIIA (CD32), uPAR (urokinase-type plasminogen activator receptor; CD87), CD14, voltage-gated K+channels (Kv1.3), integrin-associated protein (IAP), CD98, tetraspans (TM4SF), insulin receptors, and PDGFbeta receptors. In this article we will highlight certain features of this growing field of research, especially with regard to their relevance in immunology and inflammation.