Recent advances in our knowledge of the natural history of multiple sclerosis deal with the influence of pregnancy and vaccination, the predictive value of magnetic resonance imaging-based criteria in terms of activity and severity of the disease, and the weighting of the interplay between relapses and clinical progression. These advances have implications for counselling of patients and adjusting the classification of the disease course. Thus multiple sclerosis should be considered to be as much neurodegenerative as inflammatory and disease-modifying therapeutic strategies should be reconsidered by focusing on protection and repair of the nervous system.