In the last decade, the use of magnetic resonance imaging (MRI) has led to a reevaluation of the pathogenesis and the natural history of multiple sclerosis (MS). This has been driven to a significant degree by results of proton magnetic resonance spectroscopy (1H-MRS) studies. By providing evidence of early neurodegeneration (based on levels of N-acetylaspartate), results of 1H-MRS studies have led to a reconsideration of the role of axonal damage in MS. By measuring brain changes of metabolites such as choline and myo-inosol, 1H-MRS has confirmed the importance of assessing myelin damage and repair. However, despite the pathological specificity of 1H-MRS and the relatively large number of clinical 1H-MRS studies on patients with MS, measures provided by this MR technique are not used routinely for assessing and monitoring MS patients. This is due to technical difficulties and limitations that are at present not entirely solved. We will review here the most relevant results in MS studies that have used 1H-MRS measures, the clinical importance of these results and the pending issues that need to be solved for a larger and more reliable use of 1H-MRS in clinical MS studies.