Multiple system atrophy (MSA) is a neurodegenerative disease of undetermined aetiology that occurs sporadically and manifests itself as a combination of parkinsonian, autonomic, cerebellar and pyramidal signs. Despite the lack of any effective therapy to reverse this condition, some of the symptoms may be, at least temporarily, improved with adequate symptomatic therapies. Medical treatment is largely aimed at mitigating the parkinsonian and autonomic features. The therapeutic results of levodopa therapy in cases of MSA are difficult to interpret because of their variability. Nevertheless, the statement that patients with MSA are non or poorly levodopa-responsive is misleading. Clinical and pathologically proven series document about 40-60% levodopa efficacy in patients with MSA presenting with predominant parkinsonian features. Unfortunately, other antiparkinsonian compounds (dopamine agonists, amantadine) are not more effective than levodopa. Orthostatic hypotension (OH) can be suspected from the patient's history and subsequently documented in the clinic by measuring lying and standing blood pressure. The diagnosis ideally should be confirmed in the laboratory with additional tests to determine the cause and evaluate the functional deficit, so as to aid treatment. A variety of pharmacological agents with different mechanisms of action have been used in MSA to reduce OH when this is symptomatic. OH can also be alleviated by avoiding aggravating factors, such as the effects of food, micturition, exposure to a warm environment and physiological diurnal changes and by using other non-pharmacological strategies. The treatment of the very common genito-urinary symptoms (incontinence, retention, impotence) should also be considered in order to improve the quality of life of these patients.