By necessity, all anesthetic drugs produce amnesia (lack of memory) at high enough concentrations. However, certain amnesic drugs, exemplified by propofol or midazolam, produce dense amnesia at low drug concentrations while a person is still awake. This chapter reviews human memory systems, with a focus on episodic memory. This memory system is the one most affected by amnesic drugs. It is also the one most difficult to define and study in animal models. Potential mechanisms by which amnesia is produced in humans are defined in this chapter using propofol as an exemplar drug. Episodic memory is considered in terms of information flow from the outside world into long-term memory. Propofol has little effect on encoding, thus permitting memories to be formed in its presence. However, these memories are quickly forgotten, and electrophysiologic measures (event-related potentials, ERPs) of recognition memory reveal effects of propofol on memory within seconds of encoding. Potential targets for propofol’s amnesic actions on the chain of physiologic events activated by learning, termed consolidation, are discussed.