Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, associated with primary destruction of myelin sheaths. Axons are relatively well preserved, although they too are injured in the development of the lesions. While inflammation and demyelination induce neurological deficit, which is in part reversible, the destruction of axons, when past the threshold of compensation, is always accompanied by irreversible clinical deficits. The mechanisms leading to tissue injury in MS are complex and heterogenous. They involve direct cytotoxicity mediated by T-lymphocytes, specific antibodies and complement as well as toxic products of macrophages. In addition, in a small subset of patients a genetically determined increased susceptibility of the central nervous system tissue for immune mediated damage appears to play a role. Since the pathogenetic pathways of demyelination and tissue damage vary between different MS patients, their identification by paraclinical markers is of critical importance for diagnosis and therapeutic management.