Our increasing understanding of the immunopathogenesis of multiple sclerosis has led to the development of many disease-modifying therapies that have revolutionized the care of patients with relapsing forms of the disease. Our understanding of the pathophysiologic basis of progressive forms of the disease is much more limited but has dramatically changed over the past several decades. We are now on the verge of developing therapies that promote remyelination, reduce axonal loss, and restore axonal function. This progress is challenged by inadequate animal models of progressive disease and incomplete biomarkers of progression. In measuring central nervous system function, evoked potentials may have an advantage over biomarkers, which measure only pathologic change. Monitoring multifocal visual evoked potential amplitude may be one possible means of monitoring disease progression in multiple sclerosis. Additional clinical studies are required to document whether evoked potentials can adequately serve as effective biomarkers of progression.