Sudden unexpected death due to central nervous system (CNS)-related pathologies though far less common than cardiac causes still account for a substantial proportion of sudden deaths that occur worldwide. This review covers the most common causes of sudden unexpected death due to CNS-related pathologies encountered by forensic pathologists. These include intracerebral hemorrhage, aneurysmal subarachnoid hemorrhage, ischemic stroke, epilepsy, brain tumors, and infectious causes. Related rare causes are not discussed and are beyond the scope of this review. The role of neuroimaging and genetic testing as autopsy ancillary investigations in such sudden deaths is also discussed.