<p>Antibiotic stewardship is a quality improvement and patient safety initiative focused on optimizing antibiotic use to improve patient outcomes, limit the emergence of antibiotic resistance, and adverse drug effects. Here, we discuss the Centers for Diseases Control and Prevention Core Elements of Antibiotic Stewardship-leadership commitment, accountability, pharmacy expertise, action, tracking, reporting, and education-as they apply to the care of patients in the neonatal intensive care unit. Specifically, we consider neonatal intensive care unit-specific data and unique practices to frame some of the important targets necessary for successful antibiotic stewardship implementation in this setting.</p>