Memory blockade is one of the most potent and essential properties of general anesthetics. Unfortunately, some patients experience persistent memory deficits long after the anesthetic has been eliminated. Paradoxically, other patients experience inadequate memory loss leading to “intraoperative awareness”. The molecular mechanisms underlying the memory blocking properties of anesthetics remain poorly understood and have been a focus of our research. I will present studies that identify a subtype of inhibitory GABAA receptor that is highly sensitive to up-regulation by inhaled and intravenous anesthetics. The role of these receptors in normal memory processes and persistent memory deficits after exposure to anesthetics will be discussed.