Summary: The reorganization of membrane, cytoskeletal and signaling molecules during immune interactions is critical for the generation of immune response. At the initiation of the T cell–antigen presenting cell (APC) interaction, antigen-independent weak adhesion forces allow the scanning of the APC surface by the T cell receptor for specific antigens. The stabilization of T cell–APC conjugates involves the segregation of membrane and intracellular signaling proteins, driven by reorganization of membrane microdomains and cytoskeletal changes. In early T cell–APC cognate interactions, the microtubular cytoskeleton undergoes drastic changes that lead to microtubule-organizing center (MTOC) reorientation to the vicinity of the cell–cell contact area. Recent data on the dynamics of MTOC redistribution and its influence in T cell–APC conjugate stabilization, together with the description of an increasing number of signaling molecules associated to this complex, underscore the key role of MTOC translocation in the T cell response. We focus on the mechanisms that control the early MTOC reorientation during T cell–APC interaction and the relevance of this process to T cell activation.