The transdermal administration of drugs is an effe ctive alternative to conve ntional methods such as oral or subcutaneous injections, as it overcomes the difficulties associated with these routes. Several methodologies have been developed in order to enhance drug transdermal absorption. Chemical percutaneous enhancers have long been used to incr ease the range of drugs that can be effectively delivered through the skin. To date, a vast array of chemicals has been evaluated as enhancers. This chapter reviews the principal chemical percutaneous enhancers and their mechanisms of acti on. The techniques to determine permeation enhancement and their uses in topical/transdermal formulations are also discussed.