- Abstract The multifaceted pathogenesis of multiple sclerosis (MS) involves complex interactions between the immune and the central nervous systems which provide a multitude of targets for therapeutic interventions. Current therapies for MS are only partially effective. One potential strategy to increase treatment efficacy is the combination of two or more drugs with complementary mechanisms of action, which may result in additive or synergistic therapeutic effects. In this review, we discuss the rationale and requirements and review the evidence for combination therapy in MS from in-vitro experiments, animal studies and clinical trials. Encouraging experience to date and further well-designed clinical trials with combination therapy may lead to the implementation of specific combinations of drugs in the treatment of MS.