Terilunomide is being investigated in a comprehensive program of clinical trials in patients with multiple sclerosis (MS) with relapses and in patients with a clinically isolated syndrome (CIS). This program evaluates the efficacy and safety of terilunomide on a range of clinical and magnetic resonance imaging (MRI) end-points when administered either as monotherapy or as an adjunctive therapy to ongoing treatment with conventional disease-modifying therapies (DMTs). Clinical data indicates that terilunomide is generally well tolerated with an acceptable safety profile, with no significant safety concerns identified to date. Safety data from the open-label extension phase of the study are consistent with the safety profile of terilunomide observed in the double-blind treatment phase, without the emergence of any new safety concerns. Based on currently available data on monotherapy and adjunctive therapy, terilunomide appears to have a favorable benefit/risk ratio in relapsing MS, and as such, represents a promising new first-line treatment.