Multiple system atrophy is a rare condition of the nervous system that causes gradual damage to nerve cells in the brain and spinal cord and progressive loss of associated functions. It is a member of a class of neurodegenerative diseases known as synucleinopathies that have in common an abnormal accumulation of the alpha-synuclein protein in various parts of the brain. The hallmark of the disease is the widespread inclusions of misfolded alpha-synuclein protein - the same protein involved in Parkinson's disease. This book will describe the clinical presentations of the disease, types and variants, diagnostic tests used, drugs employed, and therapies administered. The tests can only help determine whether the diagnosis is 'probable' or 'possible' since no laboratory or imaging studies are able to definitively confirm the diagnosis and there are no useful biomarkers. No test can provide a definitive diagnosis, which remains challenging and difficult in part because of many confounding diseases. Because of this difficulty, some people are actually never properly diagnosed or may not ever be diagnosed. The portfolio of the majority of the developed therapeutic approaches is presented. It includes the panoply of drugs, clinical trials, and the newer modalities of immunotherapy, gene therapy, and mesenchymal stem cell therapy. Unfortunately, there is no cure as the alpha-synuclein processes are only symptoms, not the root cause(s), of the disease so the proximal trigger remains unknown. Regardless, while prognosis and future outlook are poor, there is valuable support from numerous advocating and supporting organizations. There is also hope for the future as research has made excellent progress, especially in the development of new treatment options. A shift in thinking about the disease is still needed with greater consideration given to the potential underlying degenerative etiology that will eventually unravel the mystery and provide a cure.