We provide a focused review of novel immunomodulatory approaches for the treatment of multiple sclerosis, the most common acquired inflammatory demyelinating disease of humans. The requirement for such a review was stimulated by the emerging application of novel oral medications and the need for the practicing physician to place these within the treatment paradigm. We provide a conceptual diagram of our current view of the pathogenesis of demyelination and remyelination in this disorder. In addition, we include a working template on how to use a tier 1 and tier 2 approach to medications as the disease worsens in the individual. We emphasize the approach of treatment based on "individualized medicine," tailored to the specific needs of each patient. In the future, we envision new drugs to enhance remyelination and protect neurons and axons from death in order to promote central nervous system regeneration and repair.