Clinical decision support systems (CDSSs) are entities that intend to support clinical personnel in medical decision-making tasks. In more technical terms, CDSSs are active knowledge systems that use two or more items of patient data to generate case-specific advice. CDSSs first appeared in the late 1950s but have experienced significant growth over the last three decades providing advice in the clinical decision-making process. Specific fields of decision support offered by CDSSs include diagnosis, therapy planning, alerting and informing, and information retrieval. CDSSs interact with patient records and measurement devices for data acquisition and knowledge bases for retrieval of knowledge related to the specific case. Combining the data from the above sources, intelligent methods are applied for clinical inference. Rule-based, probabilistic, and machine learning techniques are employed to provide reliable results to support medical decisions. Recent and forthcoming advances in information technologies are expected to foster CDSSs applied in clinical practice.