Antibiotic overuse contributes to antibiotic resistance, which is a threat to public health. Antibiotic stewardship is a practice dedicated to prescribing antibiotics only when necessary and, when antibiotics are considered necessary, promoting use of the appropriate agent(s), dose, duration, and route of therapy to optimize clinical outcomes while minimizing the unintended consequences of antibiotic use. Because there are differences in common infectious conditions, drug-specific considerations, and the evidence surrounding treatment recommendations (eg, first-line therapy, duration of therapy) between children and adults, this statement provides specific guidance for the pediatric population. This policy statement discusses the rationale for inpatient and outpatient antibiotic stewardship programs; essential personnel, infrastructure, and activities required; approaches to evaluating their effectiveness; and gaps in knowledge that require further investigation. Key guidance for both inpatient and outpatient antibiotic stewardship programs are provided.