Multiple system atrophy (MSA) is a neurodegenerative disease that presents as an autonomic dysfunction in combination with varying degrees of parkinsonism and cerebellar ataxia. It comprises a pathologically widespread neuronal loss accompanied by gliosis in the basal ganglia, cerebellum, pons, inferior olivary nuclei, and spinal cord. As a rapidly progressive disorder, MSA develops with autonomic dysfunction and mobility problems in several years. These autonomic and motor function impairments severely disrupt the patients' daily lives. Currently, the therapeutic management of this disease is only symptomatic. An early and accurate diagnosis is helpful not only in the clinical field but also in the research for new therapies. The biomarkers in cerebrospinal fluid (CSF) and serum facilitate the differential diagnosis of MSA when the disease is difficult to recognize based on the clinical features or even presymptomatic. This review will summarize the biomarkers present in CSF that are potential candidates to accurately differentiate MSA from other similar neurodegenerative disorders.