<p>Antimicrobial medications are the most commonly used medications in the neonatal intensive care unit. Antibiotics are used for infection prophylaxis, empiric treatment, and definitive treatment of confirmed infection. The choice of medication should be informed by the epidemiology and microbiology of infection in specific clinical scenarios and by the clinical condition of the infant. Understanding evolving pathogen susceptibility to antimicrobials and key pharmacotherapy determinants in neonates can inform optimal antibiotic use.</p>