Every year thousands of children undergo surgery for congenital heart disease. Cardiac surgery requires the use of cardiopulmonary bypass, which can have unexpected consequences for pharmacokinetic parameters. We describe the pathophysiological properties of cardiopulmonary bypass that may influence pharmacokinetic parameters, with a focus on literature published in the last 10 years. We performed a PubMed database search with the keywords 'Cardiopulmonary bypass' AND 'Pediatric' AND 'Pharmacokinetics'. We searched related articles on PubMed and checked the references of articles for relevant studies. Interest in the influence of cardiopulmonary bypass on pharmacokinetics has increased over the last 10 years, especially due to the use of population pharmacokinetic modeling. Unfortunately, study design usually limits the amount of information that can be obtained with sufficient power and the best way to model cardiopulmonary bypass is yet unknown. More information is needed on the pathophysiology of pediatric heart disease and cardiopulmonary bypass. Once adequately validated, PK models should be integrated in the patient electronic database integrating covariates and biomarkers influencing PK, making it possible to predict real-time drug concentrations and guide further clinical management for the individual patient at the bedside.