Transdermal drug delivery system offers an alternative pathway for systemic drug delivery with several advantages over conventional routes. Unfortunately, the barrier nature of the skin presents a significant obstacle for most drugs to be delivered. Consequently, several approaches including both the chemical and physical enhancement strategies are used to increase skin permeability. Potential substances used for this purpose need to have both features, i.e. drug penetration-promoting effects and a low or no skin irritating potential. However, none of the chemical penetration enhancer exhibits both of these properties. Physical methods involving ultrasound, electric fields, magnetic field, pressure waves, radiofrequency, abrasion, have more extensively increased transdermal delivery for small drugs, macromolecules and vaccines. The ability of these technologies to deliver drugs effectively is partially counterbalanced by their reliance on electronically controlled devices, which constrains applications and cost. This book therefore provide an insight of the penetration enhancement techniques useful for delivery of drug across skin overcoming its barrier function.