Clinical decision support systems have been increasingly utilized in the healthcare industry to improve patient outcomes and enhance clinical decision-making, taking advantage of the growing digital medical data. Despite their potential, there are still obstacles in an extensive adoption of these systems, such as low usability and human factors. In this systematic review, several articles describing clinical decision support systems with clinical validation are used to address some of the gaps, as well as to map the current academic landscape for the given context. The selected articles are observed through a Human-Computer Interaction perspective, aiming to identify the state-of-the-art, as well as barriers to the application of these principles. From an initial database search resulting in 121 articles, 16 articles were selected that fulfilled the chosen criteria: (1) article must be available and written in English, (2) article must report experimental work, (3) the reported system must be clinically validated. The research strategy followed the PRISMA framework. We highlight the need for clinical validation, a standardized clinical decision support taxonomy and the evaluation of these tools across multiple variables. Based on the found results, a list of recommendations can be formed to aid the development of future CDSS, or the improvement of current ones.