Clinical decision support (CDS) includes a variety of tools and interventions computerized as well as non- computerized. High-quality clinical decision support systems (CDSS), computerized CDS, are essential to achieve the full benefits of electronic health records and computerized physician order entry. A CDSS can take into account all data available in the EHR making it possible to notice changes outside the scope of the professional and notice changes specific for a certain patient, within normal limits. However, to use of CDSS in practice, it is important to understand the basic requirements of these systems.This chapter shows in what way CDSS can support the use of clinical data science in daily clinical practice. Moreover, it explains what types of CDSS are available and how such systems can be used. However, to achieve high-quality CDSS which is effective in use requires thoughtful design, implementation and critical evaluation. Therefore, challenges surrounding implementation of a CDSS are discussed, as well as a strategies to develop and validate CDSS.