Multiple sclerosis (MS) remains a major challenge to basic and clinical research. Some of the pivotal immune mechanisms operating in this chronic inflammatory disease have recently been characterized but development of more satisfactory treatment still requires a better understanding of the pathogenesis and immunopathology of MS. Adhesion molecules are known to be of fundamental importance in autoimmune disease, and a variety of new therapeutic approaches to target them have emerged in the past few years; they should open new avenues to improve the outcome of this disabling disease.