Cerebrospinal fluid (CSF), with its protein markers, is a formidable material for investigating the relationships among the various cell types involved during the initial phase of plaque formation, or, successively, in the remyelination process. Its analysis may give definite help in better focusing on therapeutic objectives and therapeutic tools. Therefore, the possible use of CSF MBP, S-100, GFAP, N-CAM, NGF, and CNTF in pathogenetic studies and in clinical follow-up is critically reviewed. The need for correct interpretation of the data, for uniformity and reliability of the analytical methods, and for easy access to them is stressed. CSF examination and MRI should not be considered as alternative tools, or in competition, but should be used together, to take the maximum advantage of their individual possibilities.