Notwithstanding the availability of disease-modifying treatments including interferon-β, glatiramer acetate, and natalizumab, a considerable proportion of multiple sclerosis (MS) patients experience continued progression of disease, clinical relapses, disease activity on MRI, and adverse effects. Application of gene expression, proteomic or genomic approaches is universally accepted as a suitable strategy toward the identification of biomarkers with predictive value for beneficial/poor clinical response to therapy and treatment risks. This review focuses on recent progress in research on the pharmacogenomics of disease-modifying therapies for MS. Although MS drug response biomarkers are not yet routinely implemented in the clinic, the diversity of reported, promising molecular markers is rapidly increasing. Even though most of these markers await further validation, given time, this research is likely to empower neurologists with an enhanced armamentarium to facilitate rational decisions on therapy and patient management.