Clinical decision support (CDS) systems are an increasingly used form of technology designed to guide health care providers toward established protocols and best practices with the intent of improving patient care. Utilization of CDS for infection prevention is not widespread and is particularly focused on antimicrobial stewardship. This article provides an overview of CDS systems and summarizes key attributes of successfully executed tools. A selection of published reports of CDS for infection prevention and antimicrobial stewardship are described. Finally, an individual organization describes its CDS infrastructure, process of prioritization, design, and development, with selected highlights of CDS tools specifically targeting common infection prevention quality improvement initiatives.