Increasing evidence indicates that blood platelets contribute to diverse processes that extend beyond hemostasis. Many of the same mechanisms that play a role in hemostasis and thrombosis facilitate platelets the participation in other physiological and pathological processes, particularly in the inflammation, the immune response and central nervous system disorders. Platelets are involved in pathophysiology of central nervous system diseases, especially in the pathogenesis of multiple sclerosis, but their role appears to be neglected. Platelets contribute to the inflammation and cooperate with immune cells in inflammatory and immune responses. These blood cells were identified in inflamed spinal cord and in the brain in chronic active lesions of multiple sclerosis and in the related animal models referred as Experimental Autoimmune Encephalomyelitis. This review summarizes recent insights in the platelet activation accompanied by the exocytosis of bioactive compounds stored in granules, formation of platelet microparticles, expression of specific membrane receptors, synthesis of numerous biomediators, generation of free radicals, and introduces the mechanisms by which activated platelets may be involved in the pathophysiology of multiple sclerosis. Understanding the role of platelets in multiple sclerosis may be essential for improved therapies.