Transdermal route is preferred due to its numerous advantages over other routes. Stratum corneum and other skin layers are the foremost obstacles in employing skin as a drug delivery route. So various penetration enhancement techniques are utilized which cause the delivery of drug through the skin in proper amounts and at a predetermined rate. Permeation enhancers are the agents which do not have any therapeutic activity themselves but these increase the permeability of drug through the skin. Numerous chemical agents from natural and synthetic origins are evaluated for their penetration enhancement ability. Other than chemical agents, various novel drug delivery systems such as nanoparticles, liposomes, niosomes, transferosomes and ethosomes etc; and various physical means of skin ablaze are also useful for drug penetration through skin. The focus of this review is to discuss various permeation enhancement techniques for effective delivery of drugs through skin.