Their common clinical use, frequency of adverse effects, serious therapeutic indications, treatment failures, and availability of sensitive assays make corticosteroids such as prednisone and prednisolone candidates for therapeutic drug monitoring. Complicating the interpretation of plasma drug concentrations are the first-pass metabolism of inactive prednisone to active prednisolone and reconversion. Also, the volume of distribution, metabolic clearance, and renal clearance of prednisolone increase with dose. This is due partly to saturable binding of prednisolone to transcortin in plasma, which provides more unbound drug at higher plasma concentrations of steroid. This effect plus the probable uptake of only unbound drug into intracellular receptor sites provides the rationale for measuring free prednisolone in plasma. Drug interactions between prednisolone and anticonvulsants are common. Liver and kidney disease have only limited effects on prednisolone disposition. Changes in clinical efficacy and appearance of side effects have been related to altered prednisolone clearance. Plasma concentrations may be used to determine disease and drug interactions, bioavailability, and patient compliance. The role of pharmacokinetic factors in governing the indirect and variable pharmacodynamic response to corticosteroids at various tissue sites and in disease states currently needs clarification.