The poor penetration of drugs into the skin (and, partially, the permeation across the stratum corneum) often limits the efficacy of topical formulations. Basically, skin penetration can be enhanced by the following strategies: (i) increasing drug diffusivity in the skin; (ii) increasing drug solubility in the skin, and/or (iii) increasing the degree of saturation of the drug in the formulation. In this article, we review the literature with respect to: (i) chemical penetration enhancers, which have been shown to influence the diffusivity and/or solubility of the drug in the skin and (ii) supersaturated formulations, in which the degree of saturation of the drug is increased compared to conventional formulations. In addition, three different in vitro methods, specifically, classic diffusion cell studies, attenuated total-reflectance-Fourier transform infrared spectroscopy, and tape stripping in conjunction with an appropriate analytical technique, are considered, emphasizing their application to obtain quantitative values for skin transport parameters and to separate the kinetic or thermodynamic effects of an enhancement strategy.