Transient global amnesia syndrome was initially described more than a century ago. Although the clinical syndrome is easily recognized and highly consistent in its characteristic features, the underlying pathophysiology has remained elusive. Proposed mechanisms include focal ischemic lesions or local nonischemic energy failures. Diffusion-weighted imaging has been able to demonstrate focal areas of restricted diffusion. Nonetheless, the mechanism of this diffusion restriction is uncertain and does not necessarily indicate ischemia, leaving the exact nature of this seemingly benign disorder in doubt. This review summarizes the pertinent clinical features, proposed pathophysiology, epidemiology, imaging, and future directions in understanding transient global amnesia. © 2011 Elsevier Inc.