Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS) manifested by heterogeneous group of neurological symptoms. Progression of disease may eventually lead to severe disability. It is more common in young adults, while females are predominantly affected. Although etiology of MS remains unknown, it is certain that genetic and environmental factors play important roles. Pathologically, MS is characterized by multifocal demyelinated inflammatory lesions of the CNS. Although some lesions do appear in grey matter, most lesions appear in the white matter of the brain, most notably in the optic nerves, the brainstem, the spinal cord and in the periventricular zones. According to histologic criteria, the CNS lesions in MS are classified as acute, chronic active and chronic inactive plaques. On histological sections these plaques exert an inflammatory infiltrate consisting of T cells, B cells and macrophages. However, recent histopathological studies of MS lesions revealed a great variability within lesions of different subjects with respect to the extent of inflammation, oligodendrocyte pathology and neuroaxonal injury. Demyelination, followed by a variable degree of remyelination, is associated with oligodendrocyte loss during the chronic stage of the disease. Axonal loss and gliosis with astrocyte proliferation and glial fiber production are also important pathologic features of MS. There is an increasing evidence that neuroaxonal damage is a key feature in MS lesions and that it has a major impact on permanent neurologic deficits. Hence, in the past few years an increasing improvement of laboratory and imaging approaches to study MS lead to a better understanding of the immuno-pathogenesis, pathology and etiology of this severe disease.