From 1983 to 1998, U.S. fatalities from acknowledged prescription errors increased by 243%, from 2,876 to 9,856. This percentage increase was greater than for almost any other cause of death, and far outpaced the increase in the number of prescriptions. Many nonfatal prescription errors also occur, but estimates of the frequency of these errors vary widely, because various definitions, geographic settings, and institutions have been used. Efforts to reduce fatal and nonfatal prescription errors have encountered perceptual, legal, medical, and cultural barriers. It may be possible to reduce prescription errors by instituting a central agency responsible for collecting, analyzing, and reporting harmful or potentially harmful drug events, and for issuing recommendations and directives.