A rational goal of clinical pharmacology is to described and predict the relationship between drug dose and drug effect. The processes involved in the dose-effect relationship can be described in two main categories - pharmacokinetics, which is concerned with factors affecting the dose-active site concentration process, and pharmacodynamics, which describes the active site concentration-effect process. The development of models of the dose-effect relationship will be described starting with dose-effect models which do not distinguish between pharmacokinetics and pharmacodynamics, progressing to models based upon pharmacokinetic predictions of the active site concentration, and finally describing models which combine both pharmacokinetic and pharmacodynamic models to predict both active site concentrations and the drug effect.