The volumes of current patient data as well as their complexity make clinical decision making more challenging than ever for physicians and other care givers. This situation calls for the use of biomedical informatics methods to process data and form recommendations and/or predictions to assist such decision makers. The design, implementation, and use of biomedical informatics systems in the form of computer-aided decision support have become essential and widely used over the last two decades. This paper provides a brief review of such systems, their application protocols and methodologies, and the future challenges and directions they suggest.