Several lines of evidence suggest that gender affects the susceptibility and course of multiple sclerosis. A higher disease prevalence, as well as an overall better prognosis, in women than men is observed. This sex dimorphism may be explained by the effect of sex hormones on brain damage and repair mechanisms. Experimental, clinical and MRI evidence confirms a pathogenetic link between sex hormones and multiple sclerosis, also suggesting sex-specific effects of hormones in multiple sclerosis pathology and therapy. A gender-based approach to multiple sclerosis could provide further benefits for its treatment and management.