Antimicrobial stewardship (AS) is a program that oversees institutional antimicrobial use and can include restriction of antibiotics, subsequent de-escalation after culture results are back, optimization of dosing, and minimization of toxicity. The concept of AS is supported by many organizations, including Infectious Diseases Society of America, Society for Healthcare Epidemiology of America, and the Centers for Disease Control. The potential benefits include significant cost savings, decrease in the rate of resistance, lower incidence of Clostridium difficile-associated diarrhea, and shorter hospital length of stay. Typically, an AS committee will include an infectious disease physician, pharmacist, and informatics specialist and will need close relationships with the microbiology lab and infection control. To be successful, the hospital administration must be supportive, and community physicians must buy into the concept. Besides antibiotic restriction and de-escalation after culture results are back, potential areas for cost savings include: surgical prophylaxis, limiting the course of antibiotics in ventilator-associated pneumonia, dosing aminoglycosides properly, eliminating redundant antibiotics, and changing from intravenous to oral agents in a timely manner. Newer diagnostic methods such as polymerase chain reaction to quickly characterize gram positive cocci, can also be used to optimize antibiotic use. Computer systems have a promising role in AS.