The knowledge of characteristic lesion patterns is important in daily practice imaging, as the radiologist increasingly is required to provide precise differential diagnosis despite unspecific clinical symptoms like cognitive impairment and missed elaborated neurological workup. This part II dealing with nonvascular white matter changes of proven cause and diagnostic significance aimed to assist the evaluation of diseases exhibiting lesions exclusively or predominantly located in the white matter. The etiologies commented on are classified as follows: (a) toxic-metabolic, (b) leukodystrophies and mitochondriopathies, (c) infectious, (d) neoplastic, and (e) immune mediated. The respective mode of lesion formation is characterized, and typical radiological findings are displayed. More or less symmetrical lesion patterns on the one hand as well as focal and multifocal ones on the other are to be analyzed with reference to clinical data and knowledge of predilection sites characterizing major disease categories. Complementing spinal cord imaging may be useful not only in acute and relapsing demyelinating diseases but in certain leukodystrophies as well. In neuromyelitis optica (NMO), the detection of a specific antibody and some recently published observations may lead to a new understanding of certain deep white matter lesions occasionally complicating systemic autoimmune disease.