Transdermal drug delivery system has been accepted as potential non-invasive route of drug administration, with advantages of avoidance of the first-pass metabolism, sustained therapeutic action and better patient compliance, though, its prevalent use is restricted due to excellent impervious nature of skin. It is the greatest challenge for researchers to surmount the inherent limitations imposed by stratum corneum of skin, for enhanced transdermal drug delivery to achieve systemic therapeutic concentration. Thus, many approaches have been attempted to perturb skin barrier and enhance the transdermal delivery of drug. The major approaches for enhancing transdermal delivery are physical enhancers (ultrasound, iontophoresis, electroporation, magnetophoresis, microneedle), vesicles, particulate systems (liposome, niosome, transfersome, microemulsion, solid lipid nanoparticle) and chemical enhancers (sulphoxides, azones, glycols, alkanols, terpenes etc.). The present review explores recent patents on techniques employed to breach the skin barrier for drug permeation along with their penetration enhancement mechanisms.