The skin offers an enticing portal for the noninvasive delivery of selected novel and existing therapeutics. This review sheds light on the factors that must be considered in the rational design and selection of a transdermal therapeutic agent: the biological nature of the barrier, the balance between the physicochemical properties of the membrane and the drug, and the technologies available to the pharmaceutical scientist to facilitate transport. The authors also describe the recently developed technique of “reverse iontophoresis” and the potential for noninvasive biologic monitoring via the skin.