MSA is a progressive neurodegenerative disorder characterized by autonomic failure and a variable combination of poor levodopa-responsive parkinsonism and cerebellar ataxia (CA). Current therapeutic management is based on symptomatic treatment. Almost one third of MSA patients may benefit from l-dopa for the symptomatic treatment of parkinsonism, whereas physiotherapy remains the best therapeutic option for CA. Only midodrine and droxidopa were found to be efficient for neurogenic hypotension in double-blind, controlled studies, whereas other symptoms of autonomic failure may be managed with off-label treatments. To date, no curative treatment is available for MSA. Recent results of neuroprotective and -restorative trials have provided some hope for future advances. Considerations for future clinical trials are also discussed in this review.