Studies that examine the pharmacokinetics of topical drugs at their site of action in the skin have been difficult to perform and, therefore, limited in number. In the early years of topical drug pharmacokinetic research, investigators had to rely on the measurement of less direct indicators of drug throughput such as blood levels and urinary excretion. Today, advances in theory are impelling pharmacokinetic research in new directions, including the measurement of drug availability in tissue compartments within the skin. This research will lead to greater precision in pharmacokinetic measurement and greater relevance of these measurements to the therapeutic efficacy of topical cortico-steroids in cutaneous disease states.