Pharmacokinetics and pharmacodynamics data are often analysed by mixed-effects modelling techniques (also known as population analysis), which has become a standard tool in the pharmaceutical industries for drug development. The last 10 years has witnessed considerable interest in the application of experimental design theories to population pharmacokinetic and pharmacodynamic experiments. Design of population pharmacokinetic experiments involves selection and a careful balance of a number of design factors. Optimal design theory uses prior information about the model and parameter estimates to optimize a function of the Fisher information matrix to obtain the best combination of the design factors. This paper provides a review of the different approaches that have been described in the literature for optimal design of population pharmacokinetic and pharmacodynamic experiments. It describes options that are available and highlights some of the issues that could be of concern as regards practical application. It also discusses areas of application of optimal design theories in clinical pharmacology experiments. It is expected that as the awareness about the benefits of this approach increases, more people will embrace it and ultimately will lead to more efficient population pharmacokinetic and pharmacodynamic experiments and can also help to reduce both cost and time during drug development. Copyright © 2008 John Wiley & Sons, Ltd.