Our incomplete understanding of the developmental maturation of drug elimination mechanisms poses a serious challenge to paediatric dosage regimen design and toxicological risk assessment. The dynamic and variable nature of maturation also limits our ability to acquire pharmacokinetic data in all relevant paediatric populations. However, recent attempts to use the available human ontogeny data to build predictive models of paediatric drug elimination hold promise to assist dosage regimen design and risk assessment. This review identifies population pharmacokinetic, allometric scaling and physiologically based clearance scaling models as principal approaches to estimate paediatric systemic clearance in the absence of comprehensive age-group-specific data.