Multiple sclerosis is an autoimmune disease that commonly affects young adults. If initially characterized by acute relapses, it is later followed by only incomplete remission. Over years, progressive disability and irreversible deficit lead to chronic neurological deficits in the majority of patients. The clinical course is protracted and unpredictable, and no biological marker is useful in predicting the evolution of autoaggression and disability. It is difficult to diagnose and to monitor disease progression after the initial symptoms or even during the major clinical manifestations, and it is difficult to treat. In this review, the authors report recent advances in the field, focusing on the search of new antigens as a marker of the disease, in their relevance to the pathophysiology and diagnosis of the disease.