Transient amnesic syndromes are striking clinical phenomena that are commonly encountered by physicians in acute medical settings. Diagnosis of such syndromes can be challenging, and their causes have been debated for over 50 years. Critical clinical distinctions, such as between transient global amnesia (TGA) and transient epileptic amnesia (TEA), as well as important clues to the underlying pathophysiology, have recently been revealed. TGA is characterized by the sudden onset of a profound anterograde and retrograde amnesia that lasts for up to 24 h, with neuroimaging after an acute TGA event showing transient perturbation of specific hippocampal circuits that are involved in memory processing. Some cases of transient amnesia are attributable to focal seizure activity and are termed TEA, which has a clinical presentation similar to that of TGA, but can be distinguished from the latter by the brevity and frequency of amnesic attacks. Moreover, TEA carries a risk of persistent memory impairment that can be mistaken for dementia. Here, we summarize clinically relevant aspects of transient amnesic syndromes, giving practical recommendations for diagnosis and patient management. We describe results from imaging and epidemiological studies that have shed light on the functional anatomy and pathophysiological mechanisms underlying these conditions.