Until very recently, the only drugs that could permeate transdermally were those possessing a very narrow and specific combination of physicochemical properties. However, rapid advances in bioengineering have led to the emergence of various new “active” enhancement technologies designed to transiently circumvent the barrier function of the stratum corneum. These novel systems, using iontophoresis, sonophoresis, electroporation, or microneedle arrays, will greatly expand the range of drugs that can be delivered transdermally. Crucially, the delivery of macromolecules will become possible and the transdermal flux of other molecules could be enhanced by several orders of magnitude. This article sequentially reviews the basis of each of the new enhancement techniques and discusses how these emerging technologies will influence transdermal therapy in the coming years.