This chapter on “Selective Vulnerability” examines the selective vulnerability of different parts of the brain to particular diseases. In one disease, certain areas of brain are particularly vulnerable. In other diseases, different parts of the brain are more susceptible. The concept of selective vulnerability was originally applied to toxic/metabolic and hereditary disorders, but it is also useful in thinking about other neuropathologic processes including neoplastic, infectious, demyelinative, vascular, and traumatic diseases. Diseases can selectively affect brain systems, brain structures, or brain regions. Selective system involvement is clear in degenerative diseases such as amyotrophic lateral sclerosis; selective structure involvement occurs in carbon monoxide’s effect on the globus pallidus; selective region involvement is found in myelinolysis.