BACKGROUND Whole-body physiologically-based pharmacokinetic (WB-PBPK) models mathematically describe an organism as a closed circulatory system consisting of compartments that represent the organs important for compound absorption, distribution, metabolism and elimination. OBJECTIVE To review the current state of WB-PBPK model use in the clinical phases of drug development. METHODS A qualitative description of the WB-PBPK model structure is included along with a review of the varying methods available for input parameterisation. Current and potential WB-PBPK model application in clinical development is discussed. CONCLUSIONS This modelling tool is at present used for small and large molecule drug development primarily as a means to scale pharmacokinetics from animals to humans based on physiology. The pharmaceutical industry is active in employing these models to clinical drug development although the applications in use now are narrow in comparison to the potential. Expanded integration of WB-PBPK models into the drug development process will only be achieved with staff training, managerial will, success stories and regulatory agency openness.