Purpose of the Review <p>This review highlights the importance and benefits of antimicrobial stewardship (AMS) in neonatal intensive care units (NICUs), where antibiotic overuse is common despite low rates of culture-proven infection. It explores the impact of AMS on clinical outcomes, antimicrobial resistance, and healthcare resource utilization.</p> Recent Findings <p>Evidence shows that AMS programs reduce antibiotic use, hospital length of stay, and incidence of complications such as necrotizing enterocolitis (NEC) and secondary infections. They also mitigate antimicrobial resistance, reduce toxicity, and preserve the neonatal microbiome, important for long term health benefits. Risk stratification tools, microbiological data integration, and diagnostic stewardship support targeted therapy without compromising safety. Recent studies confirm that shorter empirical courses and narrow-spectrum antibiotics do not increase sepsis or mortality risk. Cost analyses show favorable economic impact, and strategies like “handshake” stewardship and early cessation of antibiotics are effective but require institutional commitment with sufficient staff support and financial input.</p> Summary <p>AMS in NICUs is essential for balancing the risks of undertreating infections with the harms of overuse. Interventions improve outcomes, preserve microbiome integrity, and reduce resistance and healthcare costs. Despite implementation challenges, strong interdisciplinary collaboration and robust clinical tools can drive effective stewardship. A culture of judicious antibiotic use is critical to safeguarding neonatal health and antibiotic efficacy.</p>