The immune synapse can be compared to a molecular machine that controls T cell activation when getting in contact with an antigen-presenting cell (APC). The immune synapse is involved in the transfer of information across the T cellAPC junction. It plays an essential role in the control and nature of the immune response. In recent years several approaches have been developed to reprogram the immune response by targeting molecules involved in the immune synapse. Monoclonal antibodies, such as those targeting the lymphocyte co-receptor, costimulatory and adhesion molecules (CD3, CD4, CD40L, CTLA4-Ig, LFA-1), or altered peptide ligands have been shown capable of inducing immune tolerance in transplantation, autoimmunity and allergy. This volume discusses the progress in the field, from basic science to clinical trials, and the major mechanisms involved. It is of interest to clinicians and researchers working in this area.