The increasing availability of new agents to treat multiple sclerosis poses new challenges for clinicians who seek therapies that are both safe and effective for their patients. The introduction of additional effective therapies has been accompanied by the recognition of serious side effects. The clinician now must weigh both the benefits and risks of therapies to help patients decide which treatment best fits each patient׳s risk/benefit profile. An optimal selection of therapies relies on a complete understanding of the risks of therapies and the factors that may help evaluate and mitigate those risks. An individualized treatment approach that incorporates patient and disease factors is needed for each patient. In this review we present risk stratification and mitigation strategies of disease modifying agents for multiple sclerosis.