Health care-associated infections (HAIs) are a leading cause of in-hospital mortality and adverse events such as antimicrobial resistance. These infections place tremendous burdens on the health care system and create situations for misuse of antimicrobial drugs. Recognition of these factors has led professional societies, clinicians, and hospitals to develop programs to improve the management of HAIs and the use of antimicrobial drugs. The clinical literature is replete with examples of these programs, often referred to as antimicrobial stewardship. Traditionally, antimicrobial stewardship programs have relied on manual methods combined with clinical oversight and intervention. The advent of modern health care information technology offers the opportunity to expand the breadth and depth of these programs. Expert clinical decision support systems are the most promising of these information technology advances.