Multiple sclerosis (MS) is a highly heterogeneous disease. Currently, a combination of clinical features, MRI, and cerebrospinal fluid markers are used in clinical practice for diagnosis and treatment decisions. In recent years, there has been considerable effort to develop novel biomarkers that better reflect the pathologic substrates of the disease to aid in diagnosis and early prognosis, evaluation of ongoing inflammatory activity, detection and monitoring of disease progression, prediction of treatment response, and monitoring of disease-modifying treatment safety. In this review, the authors provide an overview of promising recent developments in diagnostic, prognostic, and disease-monitoring/treatment-response biomarkers in MS.