Several processes are presumed to sequentially or simultaneously contribute to the pathophysiology of multiple sclerosis (MS). Biomarkers indicative of these processes would hold great potential for (1) MS diagnostics and identification of disease stages and subcategories; (2) prediction of onset and disease course; (3) treatment selection and improved prognosis of treatment success; and (4) the evaluation of novel therapeutics. Though it is unlikely that any one marker could function as a true surrogate or stand alone, biomarker combinations or patterns could provide insight into the mechanism of action of a drug and could suffice for the pre-screening of prospective therapeutics. This publication examines the potential of biomarkers in the context of MS. It explores the current state of biomarker research for MS, barriers to progress and possible solutions and priorities. Many biomarkers are covered that are relevant to disease processes such as inflammation, axonal damage, demyelination, oxidative stress and remyelination. Individual biomarkers and biomarker approaches are discussed on their usefulness for the advancement of categories 1 to 4 listed above.