Chemical penetration enhancers are utilized in topical preparations as a method for enhancing permeation of drugs across the skin. In particular, they are utilized for transdermal delivery of medications in an attempt to produce a systemic response, to avoid first-pass metabolism, and to decrease the gastrointestinal transit time observed with oral medications. A review of the selection of chemical penetration enhancers, their mechanism of action, the most common chemical penetration enhancers in each class, and alternatives will be discussed in detail.