<b><i>Background:</i></b> By combining up-to-date medical knowledge and steadily increasing patient data, a new level of medical care can emerge. <b><i>Summary and Key Messages:</i></b> Clinical decision support systems (CDSSs) are an arising solution to handling rich data and providing them to health care providers in order to improve diagnosis and treatment. However, despite promising examples in many areas, substantial evidence for a thorough benefit of these support solutions is lacking. This may be due to a lack of general frameworks and diverse health systems around the globe. We therefore summarize the current status of CDSSs in medicine but also discuss potential limitations that need to be overcome in order to further foster future development and acceptance.