Topical and transdermal drug delivery systems are designed to support the development of new and effective therapeutics. The human stratum corneum acting as a barrier for the permeation of active substances has limited the number of molecules commercially available as transcutaneous delivery systems. Several strategies have been employed over the past few decades to optimize drug delivery across the skin of several poorly permeable compounds. However, passive techniques present limited potential to facilitate the delivery of macromolecules. This drawback has given way to modification of more conventional formulations, as well as to the development of device-based physical enhancement techniques. Topical and transdermal delivery is therefore an area of research with many challenging objectives but also with great opportunities to work envisaging the patient compliance as it refers to a convenient painless non-invasive drug administration route.