Treatment of multiple sclerosis (MS) with pulses of high dose methylprednisolone (HDMP) is currently the treatment of choice for MS relapses in many parts of the world. The use of corticosteroids as a treatment for MS was first reported in 1951. There is emerging evidence regarding the benefits of HDMP administered in pulses on the course of MS, either alone or in combination with other disease modifying therapy. HDMP was found to improve Expanded Disability Status Scale (EDSS) better than placebo, with improvements primarily in pyramidal, cerebellar, and sensory systems. In general, corticosteroid toxicity is reduced with short-term pulsed administration of HDMP. Altogether, numerous clinical and magnetic resonance imaging (MRI) studies suggest that HDMP not only has transient beneficial effects on clinical relapses and established areas of inflammation and demyelination, but may also have a prolonged, dose-dependent benefit involving early events in MS lesion formation, lesion propagation, and lesion recovery.