Recent years have seen considerable evolution and increasing sophistication of our concepts of the pathophysiology of multiple sclerosis. These new notions include the increased recognition of the importance of extralesional pathology, of the interplay between inflammation and neurodegenerative changes, pathophysiological heterogeneity and additional immune cell populations contributing to disease. These advances have driven the development and evaluation of new therapeutic strategies and outcome measures for clinical trials. A sizeable number of new immunomodulatory and immunosuppressive agents are under development and attracting great attention. These may offer potential advantages over existing treatments in terms of convenience and efficacy, but certain agents may raise safety concerns. In addition, neuroprotective and repair strategies are beginning to be considered. Not all of these agents will eventually be marketed but they will all help us gain insight into the pathophysiology of multiple sclerosis and decipher the mechanisms that underlie its heterogeneity. The place that these therapies will come to occupy in future years will depend on their relative benefits and risks.