Multiple sclerosis is an incurable condition that introduces great uncertainty into virtually all aspects of a person's life. In this Review, Simmons considers the ways in which this uncertainty is being addressed by improved diagnostic tools, advances in immunotherapy, multidisciplinary rehabilitation, community programs, and provision of information specifically designed to facilitate shared decision-making and empowerment. He discusses these issues in the context of three philosophical frameworks: the biomedical, biopsychosocial and sociopolitical models.