Adhesive interactions play important roles in coordinating T-cell migration and activation, specifically in the formation of the immunological synapse (IS), a specialized cell-cell junction. Recent demonstrations show several molecules implicated in T-cell signaling, including Vav, ADAP, and Rap-1, have major roles in integrin regulation and place adhesion molecules at center stage in addressing the question: what are the signals involved in the formation of the IS and full T-cell activation? This review focuses on the role of integrins as an essential system for both physical adhesion and signaling in T-cell activation. The role of integrins appears to be quite distinct from classical costimulation and has been largely overlooked due to the ubiquitous use of serum in lymphocyte functional assays. Each major signal transduction pathway has branches leading to the nucleus and others that feed back on cytoskeletal and membrane regulation at the IS.