Demyelinating diseases of the central nervous system (CNS) include a number of diseases whose main feature is damage to the myelin sheath, i.e. demyelination of nerve fibers in the brain, spinal cord or optic nerves. Loss of myelin sheath leads to neurological deficits due to difficulty in conduction of electrical impulses and the clinical picture is varied because it depends on the localization and distribution of demyelinating lesions. According to the etiology, they are divided into primary (idiopathic) in which the etiology remains unknown, and secondary in which the cause is known. Primary CNS demyelinating diseases include multiple sclerosis, acute disseminated encephalomyelitis, acute hemorrhagic leukoencephalitis, neuromyelitis optica, optic neuritis, and transverse myelitis. Secondary CNS demyelinating diseases can be caused by a variety of causes, of which infections are among the most common. Infectious agents lead to demyelination of the CNS by direct or indirect mechanisms. The direct mechanism involves the invasion of the pathogen into the CNS while the indirect, which is more common, is mediated by immune mechanisms, most commonly by stimulating autoimmune reactions of the immune system due to molecular mimicry between pathogen antigen and myelin antigen in the CNS. Numerous studies have shown the existence of cross-reactivity between infectious agents and myelin antigens and therefore it is considered that infectious agents play an important etiopathogenetic role in the development of primary demyelinating diseases of the CNS as well. The aim of this study was to sistematically analyze individual pathogens including bacteria, viruses, fungi, and parasites that are being associated with primary and secondary demyelinating diseases of the CNS, explain the potential etiopathogenetic mechanisms by which they lead to demyelination and emphasize the importance of infectious etiology in the differential diagnosis of CNS demyelinating diseases.