PK/PD modelling will play an increasingly important role in drug development, because it will identify key properties of a drug in vivo, allowing the characterization and prediction of the time course of drug effects under physiological and pathological conditions (intensity and duration). It has developed from a descriptive to a mechanism-based approach, taking the relevant processes on the causal path between drug administration and drug effect into account. Recent developments and insights from systems biology and systems pharmacology will provide new information on the complexities of disease associated with the identification of multiple targets for drug treatment. This will give rise to new opportunities of drug combinations, which can only be developed rationally through the appropriate application of dynamical systems-based PK/PD models.