The neonate is physiologically and pharmacologically unique, a fact that is frequently overlooked when physicians prescribe antimicrobial therapy during the neonatal period. Pharmacology, clinical efficacy, and safety must be defined for every drug prior to routine use in newborn and young infants. Recommendations for dosage and frequency of administration for the six most commonly used antibiotics in neonates are reviewed. These dosage schedules are based on pharmacokinetic data and have proved to be safe and effective in the therapy of neonatal bacterial infections. All infants receiving antibiotics should be carefully examined for possible toxic effects due to these drugs.