 BACKGROUND Approximately 60 of drugs are used off--label in critically ill neonates in the Neonatal Intensive Care Units NICU. This is even more true for pre--term born neonates in whom pharmacokinetics of these agents may be different due to immature elimination pathways. The lack of sufficient data about efficacy and safety of many of these drugs makes it difficult to have evidence based dosing guidelines for these agents. Therefore the urge for drug research in this population is of great importance. The pharmacokinetic PK and pharmacodynamic PD characteristics of drugs in premature infants are different from the characteristics found in term neonates, older children and adults. These differences are caused among others by a different body composition, by immaturity of the renal excretion systems, the metabolic pathways in the liver and other organ functions as well as immature drug receptors and transporters. After birth, there is a rapid development of many of these functions, necessitating frequent adaptation of dosage guidelines in the first few weeks of life. Besides age and size, co--morbidity, co--administration of drugs and genetic heterogeneity may further contribute to this extensive inter--individual variability in pharmacokinetics and pharmacodynamics of premature infants. There is a critical lack of evidence--based data of drug dosing in extremely preterm neonates. 