A decade ago, the term knowledge-based system was just beginning to be used to characterize a set of prototype systems that relied for their reasoning on detailed knowledge of a domain. Biomedical problems proved particularly useful in demonstrating both the feasibility and advantage of this new approach. Today, knowledge-based systems cover a wide range of classification, interpretation, planning, and design problems, and span almost every conceivable domain of science and engineering, as well as business and management. Biomedicine, as a domain, continues to provide a fertile source of new and challenging problems. A historical development of knowledge-based systems in biomedicine is presented.