The application of therapeutic agents to the skin addresses three general objectives: (a) the treatment of a variety of dermatologic diseases: (b) the “targeted” delivery of drugs to deeper subcutaneous tissues, with a concomitant reduction in systemic exposure; and (c) so-called transdermal admin-istration to elicit a systemic pharmacological effect. Recently, significant progress towards all three goals has been recorded, and the level of research and development activity remains high. We aim to discuss these advances from mechanistic and clinical standpoints. For the topical treatment of skin disease, novel vehicles (e.g., stabilized, supersaturated systems and liposomal formulations) have led to dramatic improvements in local drug bioavailability. Transdermal delivery of drugs for systemic effect, though limited in terms of the number of compounds, is perhaps the most commercially successful (in terms of the number of products) of the controlled release technologies. Considerable activity continues to enhance drug delivery (and hence to extend the range of drugs for which transdermal delivery can be used). Existing patches use formulations that contain solvents and adjuvants capable of reducing the barrier function of the skin. Much effort is directed at iontophoresis (electrically enhanced transport), particularly for small peptides that are difficult to administer by other routes. “Reverse iontophoresis” may allow the extraction of glucose (without skin puncture) so that continuous, noninvasive monitoring of blood sugar in diabetics approaches realization. In the not too distant future, the skin may also play a role not only in drug delivery, but also with re-spect to measurements in clinical chemistry.