Transdermal drug delivery offers various advantages on skin. However, its use is limited because the presence of stratum corneum, which serve as barrier to this route. Vesicular system has potential to evade these barriers include liposome, niosome, and transfersome. Transfersome is one of vesicular systems which has highly stress-adaptive, stress-responsive complex aggregate possessing an aqueous core surrounded by complex lipid bilayer. Transfersome has some potential advantages such as the ability to deform and pass through narrow pores, serve as a carrier for both low as well as high molecular drugs. There are some theories describe which affects the formation of transfersome. Transfersome composed of amphipathic ingredient such as phosphatidylcholine, other component is bilayer softening component such as surfactant, along with lipid and surfactant, preparation method for transfersome also alcohol as a solvent in various ratio and water or phosphate buffer solution for hydration of vesicles. The mechanism behind the transfersome penetration into skin is the development of osmotic gradient because of evaporation of surface water due to body heat. There are various methods exist for the preparation of transfersome such as film dispersion method, reverse phase evaporation method, high-pressure homogenization method, and ultrasonic dispersion method. Transfersome is pertinent in the field of insulin delivery, corticosteroid delivery, delivery of protein and peptide, also serve as carrier for anticancer drug, anesthetics, non-steroidal anti-inflammatory drugs, and herbal drug.