Importance of the field:Multiple sclerosis (MS) is a neurologic disease that is the most common nontraumatic cause of serious disability in young adults.Areas covered in this review:We discuss the natural history of the disease, methods of measuring disease activity and burden, and cellular and molecular mechanisms of damage, in particular recent advances. These imply new therapeutic targets, which are beginning to be tested in animal models of MS as well as in patients.What the reader will gain:The reader will learn about some recent advances in understanding MS, especially the evolution from an inflammatory phase to a neurodegenerative phase, which have different therapeutic approaches.Take home message:MS has a long-term course of accumulating deficit in which neuroinflammation evolves into neurodegeneration, which require different treatment strategies – immune modulation and neuroprotection. Neuroprotective strategies are still under development.