The emergence of ketamine—previously known as a combat anesthetic and club drug—as a treatment for depression. Ketamine, approved in 2019 by the Food and Drug Administration for the treatment of depression, has been touted by scientists and media reports as something approaching a miracle cure. This volume in the MIT Press Essential Knowledge series chronicles the ascent of a drug that has been around for fifty years—in previous incarnations, a Vietnam-era combat anesthetic and a popular club drug—that has now been reinvented as a treatment for depression. Bita Moghaddam, a leading researcher in neuropharmacology, explains the scientific history and the biology of ketamine, its clinical use, and its recently discovered antidepressant properties, for the nonspecialist reader. Despite the excitement, Moghaddam points out, concerns exist over the unknown long-term effects of the drug; the FDA assigned ketamine a “black box” warning—its most serious safety warning. Moghaddam describes the discovery of ketamine, how it was tested on humans, and how it is used as an anesthetic, club drug, and research tool. She explains ketamine's effects on brain receptors and neurotransmitters; its emergence as an antidepressant; and theories about its antidepressant properties. Finally, she reviews safety concerns and considers future directions for research, discussing whether what we learn about ketamine will change the way we understand and treat psychiatric disorders.