The neonatal intensive care unit (NICU) presents a unique challenge within hospitals. A neonate’s response to an infectious insult is challenging to differentiate from other pathologic processes, thereby making antimicrobial management more difficult. Antimicrobial stewardship programming has sought to combat this difficulty, relying on its core principles of appropriate antimicrobial selection, dose, duration, and route of administration. Increasing evidence suggests that imprudent and prolonged use of antimicrobials can lead to various undesirable health outcomes for neonates, including necrotizing enterocolitis, disseminated fungal infection, and even death. The need for empiric antimicrobial use is unavoidable, but there are ways in which concomitant antimicrobial stewardship and infection prevention efforts can allow for optimal clinical outcomes. Pharmacy-driven stewardship efforts of optimal neonatal dosing and therapeutic drug-level management of patients in our institution’s NICU serve as examples of NICU-specific stewardship initiatives. These types of stewardship efforts function as part of a larger effort to create a culture of conscientious and judicious antimicrobial use within our NICU.