A comprehensive knowledge of the pharmacokinetics (PK) of an active pharmaceutical ingredient (API) is critical for a rapid and successful assessment of a product’s safety and efficacy. For systemically administered drug products, these PK principles are well characterized and can be broken down into absorption, distribution, metabolism, and excretion (ADME), which are then applied to assess bioavailability and bioequivalence and to develop pharmacokinetic/pharmacodynamic relationships. On the contrary, the cutaneous PK for topical drug products meant to act locally in the skin is still a gray area and thus an active research topic. This chapter reviews the various methodologies to characterize local cutaneous PK. From the early assessment of cutaneous PK via plasma and excreta sampling to infer about local cutaneous concentrations after topical drug product application to semi-invasive techniques such as dermal microdialysis and dermal open flow microperfusion. In addition, novel approaches that are on the verge of becoming widely utilized, such as microspectroscopic techniques, will also be touched upon. While there is no one-size-fits-all methodology to assess cutaneous PK after topical drug product application, it is vital to understand the advantages and disadvantages of each method, which are discussed toward the end of the chapter.