A significant incidence and prevalence of psychological disorders in multiple sclerosis (MS) has been reported. Their underlying mechanisms and the extent to which they are reactive to psychosocial factors or symptoms of the pathological process itself, remain unclear. Depression is the predominant psychological disturbance with lifetime prevalence around 50% and annual prevalence of 20%. Depression is commoner during relapses, may exacerbate fatigue and cognitive dysfunction and no firm evidence exists of its induction by interferon; instead, treating depression improves adherence to disease-modifying drugs. Anxiety is also frequent, occurs in newly diagnosed patients, and its co-morbidity with depression has been suggested to increase the rate of suicidal ideation. The relationship between stress and MS is an attractive issue because some studies pointed to an association between stressful life-events and MS onset/relapses; however, the evidence supporting this hypothesis is not conclusive so far. Other psychiatric illnesses, as bipolar affective disorder, pathological laughing and crying or psychosis occur less frequently in MS. Therapeutic strategies include psychotherapy, cognitive behavioural therapy, strengthen of coping, and specific medications. The "art" of the MS team in providing the best individualized care is emphasized, aiming to reduce the burden of the disease and improve the patients' quality of life.