At present, 10 disease-modifying therapies (DMTs) have been approved for the treatment of multiple sclerosis (MS). These therapies reduce brain lesions and relapses by targeting immune-mediated mechanisms; in some cases, they may have additional neuroprotective effects. The individual response to treatment and the adverse effect profile of these DMTs vary among patients, making treatment decisions complex. Owing to the advent of these therapeutic options and additional therapies under investigation, goals and standards for the success and failure of MS therapy need to be established. For instance, we need to have unifying standards to change medications after treatment failure. Such standards could be used in clinical trials but, more important, they could be used in the clinic—the ultimate destination of any clinical trial.