Transdermal drug delivery systems (TDDS), commonly referred to as "patches," are medication dosage forms that give a regulated release of an amount of medication that is therapeutically efficacious over a patient's skin. This chapter goes into great length into the concept of skin, drug kinetics and penetration, TDDS formulation and evaluation, and its applications. Due to its distinct advantages, such as its prolonged therapeutic effect, avoidance of first-pass metabolism, and ease of therapy termination, TDDS has attracted intentional consideration for either local or systemic drug administration for decades. Since 1980, this industry has shown tremendous progress with numerous commercial triumphs. The advancements made have been predicated on a better understanding of skin barrier function as well as the physiological, physicochemical, and pharmacokinetic aspects that support the viability of transdermal administration. The stratum corneum acted as a barrier, although appendageal and transepidermal pathways for drug delivery through skin have been discovered.