Introduction: Multiple Sclerosis (MS) is a chronic progressive course of illness that leads to the widespread pathological processes of neurodegeneration, including neuroaxonal damage, apoptosis and gliosis. Due to complex mechanisms involve in the pathophysiology of MS, finding valid biomarkers is very difficult. However, finding the effective biomarkers that are more sensitive and be able to determine the level of activity and course of the disease is necessary. Today, several biomarkers with high efficacy have been introduced to design the initial therapy, to evaluate the response to drug treatments, and to identify early diagnosis and different stages of the disease. This study was aimed to review different known biomarkers to diagnose the MS. Conclusion: The complicity of MS and the important role of biomarkers in the diagnosis of MS focus lead to several studies to evaluate the most effective biomarkers. The findings indicate that the cerebrospinal fluid (CSF) biomarkers are more valid compared to plasma biomarkers. CSF biomarkers are not influenced by the circadian rhythm and circulate in the subarachnoid space, which is in close proximity to sites of neuroinflammatory lesions in MS. Among structural biomarkers, magnetic resonance imaging is the most practicable methods for MS diagnosis.