Due to its numerous advantages, transdermal drug delivery has attracted considerable attention in recent times. The protective barrier nature of the skin however limits the absorption of most drugs across the skin. A variety of strategies are available for the modification of the drug and/or vehicle or the composition of the stratum corneum (SC), the outermost layer of the skin, to improve the absorption of most drugs. Furthermore, various techniques are available for studying the effectiveness, mode of action and skin toxicity of the penetration enhancers. Most of the earlier reviews have focused on a certain selected aspect of transdermal drug delivery. This review presents a comprehensive account of various aspects of drug delivery by transdermal route including the various chemical and physical penetration enhancers. It also discusses the in vivo and in vitro methods of evaluating chemical enhancers , their mode of action and safety.