In an attempt to overcome limitations inherent in conventional computer-aided diagnosis, investigators have created programs that simulate expert human reasoning. Hopes that such a strategy would lead to clinically useful programs have not been fulfilled, but many of the problems impeding creation of effective artificial intelligence programs have been solved. Strategies have been developed to limit the number of hypotheses that a program must consider and to incorporate pathophysiologic reasoning. The latter innovation permits a program to analyze cases in which one disorder influences the presentation of another. Prototypes embodying such reasoning can explain their conclusions in medical terms that can be reviewed by the user. Despite these advances, further major research and developmental efforts will be necessary before expert performance by the computer becomes a reality.