The pharmacokinetics and pharmacodynamics of drugs are different in adult and paediatric populations, the latter being particularly heterogeneous. These differences in pharmacokinetics and pharmacodynamics justify specific studies but raise a number of ethical and practical issues. The main practical difficulties to circumvent while performing clinical studies in children are the invasiveness of the procedures and the obstacles to patient recruitment. The invasiveness related to pain/anxiety and blood loss precludes the performance of classical pharmacokinetic studies in children in many instances, particularly in neonates and infants. Population approaches, which rely on pharmacokinetic-pharmacodynamic modelling, are particularly appealing in paediatric populations because these models can cope with sparse data. The relevance of population approaches to investigation of the dose-concentration-effect relationships and to qualitative/quantitative assessment of factors that may explain interindividual variability has already been emphasized. The aims of this review are to summarize the currently available literature on population pharmacokinetic-pharmacodynamic studies in children and to discuss a number of recent methodological developments that may facilitate the evaluation of drugs in this population by alleviating invasiveness and, subsequently, facilitating recruitment of patients. The present survey confirms that population approaches in paediatrics have already reached a large audience and that they are mostly used for analysis of sparse data. However, pharmacokinetic-pharmacodynamic studies in children are still scarce. New classes of models may extend the scope of the use of population models in paediatrics. Kinetic-pharmacodynamic models, where use of the term 'kinetic' rather than 'pharmacokinetic' emphasizes the absence of pharmacokinetic data, are indirect models where the (unobserved) drug kinetics are described by a single compartment involving a single rate constant. These models, which alleviate the need for blood samples used for the measurement of drug concentration, may be very useful in paediatric studies. Physiological and physiopathological models also have potential applications but require further development. Because the number of measurements in a single individual needs to be limited in children, it is crucial to optimize the design of the experiment in order to avoid inaccurate and unreliable results. In this review, formal optimization and simulation to evaluate a design are presented, and specific problems raised by the application of these techniques in paediatrics are addressed. Finally, the related technique of clinical trial simulation and its applications are presented and discussed.