Therapeutic drug monitoring has been applied in several patient populations to promote safer, more effective use of drugs. The development of therapeutic ranges allows clinicians to aim for a plasma drug concentration that is usually safe and effective, and calculation of specific pharmacokinetic parameters allows selection of doses that will achieve the desired plasma concentration. This concept certainly holds true in the intensive care nursery; however, the intensity of monitoring in this setting provides opportunities for far broader applications of the information obtained from drug concentration monitoring. This review provides an overview of the complexity of and potential applications for therapeutic drug monitoring in neonates based on literature and clinical experience.