To prevent the devastating consequences of infection, most infants admitted to the neonatal intensive care unit are exposed to antibiotics. However, dosing regimens are often extrapolated from data in adults and older children, increasing the risk for drug toxicity and lack of clinical efficacy because they fail to account for developmental changes in infant physiology. However, newer technologies are emerging with minimal-risk study designs, including ultra-low-volume assays, pharmacokinetic modeling and simulation, and opportunistic drug protocols. With minimal-risk study designs, pharmacokinetic data and dosing regimens for infants are now available for ampicillin, clindamycin, meropenem, metronidazole, and piperacillin/tazobactam.