Antimicrobial prescriptions in neonatal intensive care units (NICUs) represent a point of concern for the emergence of MDROs and for morbidity associated with prolonged antibiotic exposure (e.g., invasive candidiasis, necrotizing enterocolitis, and late-onset sepsis). Antimicrobial stewardship programs (ASPs) have shown to be a valuable tool for the prevention of resistance with the goals of optimizing clinical outcomes while decreasing unnecessary prescribing. The most frequent ASP strategies include the correct collection and interpretation of microbiological specimens, prescription of the narrowest-spectrum antibiotic appropriate for a particular case, and de-escalation or discontinuation of therapy in defined situations. A robust ASP requires everyday multidisciplinary collaboration between ID physicians, neonatologist, clinical pharmacists, clinical microbiologists, infection control professionals, hospital epidemiologists, and information services specialists. Education and clinical pathways (e.g., sepsis or surgical prophylaxis pathways) are an excellent starting point if followed by proactive interventions such as prospective audits and feedback and formulary restriction with prior antimicrobial authorization. The current review outlines the problems faced in NICU antimicrobial prescribing and presents various solutions from the literature.