The delivery of drugs via skin routes has been extensively investigated. Nevertheless, clinical applications are limited by the stratum corneum (SC), the predominant barrier of the skin. One of the possibilities for increasing skin absorption or permeation of drugs is the use of nano/submicron vesicular systems. Classic liposomes are of little value as carriers for drug delivery via the skin because they do not deeply penetrate it. Only specially designed liposomes have been shown to be capable of achieving enhanced delivery. Liposomes are tiny spheres ranging in diameter from 50 nm to several microns. This review article explores the types and mechanisms involved with liposomes with nanostructures for enhancing topical or transdermal drug delivery. The incorporation of some additives such as anionic surfactants and ethanol can fluidize the phospholipid bilayers, thus increasing the depths to which liposomes can penetrate into the intercellular pathways of the skin. Hair follicles are also important for the enhancement of transdermal liposomes. Niosomes, non-ionic surfactant vesicles, are alternatives to liposomes, which are also discussed in this review. Physical methods such as iontophoresis, ultrasound, and tape-stripping can further assist the delivery of drugs encapsulated in liposomes. Recent breakthroughs with liposomes are beneficial to topically applied permeants, especially for dermatological medications, cosmetic ingredients, and protein/peptide macromolecules.