Three hepatic clearance regimes (flow-limited, general, and enzyme-limited) can be defined from a model of hepatic perfusion-elimination relationships. Substances that can be used for clearance measurements can thus be classified into three categories according to the relation between their kinetic elimination constants (Vmax, Km) and hepatic blood flow. The pathophysiologic and clinical importance of the clearance regimes is discussed with special emphasis on the effect of changes in hepatic blood flow and liver function. The criteria for choosing test substances within each regime are stated. This choice depends on the object of study for a clearance measurement (blood flow, drug elimination, liver function). Only the enzyme-limited clearance regime is suited for direct assessment of quantitative liver function ('true clearance'), while the other regimes depend more or less on blood flow.