In vitro release testing (IVRT) has long been an important tool in the quality control of topical preparations. More recently, however, a proliferation of published data on drug release from semisolid dosage forms has resulted in compelling evidence indicating the potential of IVRT to provide valuable information on formulation behaviour relating to clinical performance. Based on sound theoretical principles of drug release, resulting IVRT data can be accordingly processed to reliably assess release rates of active pharmaceutical ingredients (APIs) from topical products. IVRT has received increasing acceptance by several global regulatory agencies for use as a biowaiver for topical formulations intended for local action. Further support for the application of IVRT to assess “sameness” and differences between topical formulations can be gleaned from several product-specific guidances published by the United States Food and Drug Administration (FDA). A prerequisite for the appropriate use of IVRT to establish equivalence between topical formulations is confirmation of suitability based on an acceptable validation of the method since failure to comply with these requirements can result in erroneous approvals that may have significant implications on the clinical performance of generic products. Although clinical endpoint studies have served as the gold standard to assess the safety and efficacy of pharmaceutical products, such studies in patients are considered inappropriate to assess topical generic products for local action. Data from numerous publications clearly reinforce the potential for the use of IVRT as a biowaiver for topical products for local action. Hence, IVRT can be used as a surrogate procedure and an acceptable option to assess the bioequivalence of such products, thereby facilitating faster entry of affordable generic products into the market and obviating the need for expensive and time-consuming clinical studies in patients.