There is growing body of evidence that support an association between stressful life events and an increased risk for Multiple Sclerosis (MS) exacerbations. However, the nature of this relationship remains unclear, because of the lack of agreement about the definition of stress and/or because of research design problems. This article summarizes the psychological and biological mechanisms by which stress may impact MS progression. Findings indicate a number of factors, including stressor chronicity, frequency, severity and type, depression, anxiety, health locus of control, optimism, perceived social support, and coping strategies. Applied implications are discussed, concentrating on the need for multidisciplinary care interventions that target patients' disease symptoms.