Drug delivery through skin is an alternative route of drug delivery that is getting a fresh impetus from constantly evolving techniques for penetration enhancement and various techniques for drug development. It promises better and sustained absorption bypassing side effects and extensive metabolism encountered in conventional drug delivery techniques. A vast array of compounds and physical techniques are being used for penetration enhancement with a condition of reversible and unidirectional enhancement of penetration to ensure therapeutic and safety aspects. This work reviews the current state of permeation enhancement techniques, pros and cons of each technique and summarizes the potential offered by transdermal drug delivery system in the current era of biotechnological products.