This mini-review of scientific literature highlights novel approaches that assess bioavailability and bioequivalence of drugs using the In Vitro Permeation Test (IVPT). The test is widely applied to explore transdermal and skin permeation of drugs. IVPT is an essential tool of preclinical and regulatory quantitative assessment of the rate and extent of active substance permeation via the skin under controlled lab conditions. The interest in this approach has risen significantly in recent years, as it was necessary to develop more sensitive, reproducible and ethically acceptable methods assessing drugs for topical administration. Emphasis is given on analyzing the possibilities of IVPT to confirm bioequivalence of original and reproduced drugs and comparing the method with traditional clinical and pharmacokinetic approaches. Moreover, the existing limitations of IVPT associated with variability of biological models and complex extrapolation of the obtained data to clinical conditions are discussed. The prospects for standardization, optimization and subsequent adaptation of this method and its role in novel programs assessing quality, effectiveness and therapeutic equivalence of topical drugs have been explored.