Transdermal drug delivery (TDD) is a non-invasive route of drug administration, although its applications are limited by low skin permeability. It is an attractive alternative technique over the conventional techniques for administration of systemic approaches. For both local and systemic effects skin is the major site of application. However, to penetrate the drug through skin, stratum corneum is the main barrier. So to evade the stratum corneum and to increase the flux through skin membrane, different approaches of penetration enhancement are used. Several new active rate controlled transdermal drug delivery system (TDDS) technologies have been found, developed and commercialized for the TDD. This review presents mainly the structure of skin, routes of penetration through skin, different approaches to enhance the penetration, transdermal patches to optimize the transdermal delivery system into an effective drug delivery system.