Attempts to automate the medical decision making process have been underway for the at least fifty years, beginning with data-based approaches that relied chiefly on statistically-based methods. Approaches expanded to include knowledge-based systems, both linear and non-linear neural networks, agent-based systems, and hybrid methods. While some of these models produced excellent results none have been used extensively in medical practice. In order to move these methods forward into practical use, a number of obstacles must be overcome, including validation of existing systems on large data sets, development of methods for including new knowledge as it becomes available, construction of a broad range of decision models, and development of non-intrusive methods that allow the physician to use these decision aids in conjunction with, not instead of, his or her own medical knowledge. None of these four requirements will come easily. A cooperative effort among researchers, including practicing MDs, is vital, particularly as more information on diseases and their contributing factors continues to expand resulting in more parameters than the human decision maker can process effectively. In this article some of the basic structures that are necessary to facilitate the use of an automated decision support system are discussed, along with potential methods for overcoming existing barriers.