Rapidly progressive dementias (RPDs) are neurologic conditions that develop subacutely over weeks to months or, rarely, acutely over days. In contrast to most dementing conditions that take years to progress to death, RPD quickly can be fatal. It is critical to evaluate patients who have RPD without delay, usually in a hospital setting, as they may have a treatable condition. This review discusses a differential diagnostic approach to RPD, emphasizing neurodegenerative, toxic and metabolic, infectious, autoimmune, neoplastic, and other conditions to consider.