Background: Skin being the largest organ of the human body plays a very important role in the permeation and penetration of the drug. In addition, the transdermal drug delivery system (TDDS) plays a major role in managing dermal infections and attaining sustained plasma drug concentration. Thus, evaluation of percutaneous penetration of the drug through the skin is important in developing TDDS for human use.Material and methods: Various techniques are used for getting the desired drug penetration, permeation, and absorption through the skin in managing these dermal disorders. The development of novel pharmaceutical dosage forms for dermal use is much explored in the current era. However, it is very important to evaluate these methods to determine the bioequivalence and risk of these topically applied drugs, which ultimately penetrate and are absorbed through the skin.Results: Currently, numerous skin permeation models are being developed and persuasively used in studying dermatopharmacokinetic (DPK) profile and various models have been developed, to evaluate the TDD which include ex vivo human skin, ex vivo animal skin, and artificial or reconstructed skin models.Conclusion: This review discusses the general physiology of the skin, the physiochemical characteristics affecting particle penetration, understand the models used for human skin permeation studies and understanding their advantages, and disadvantages.