There has been increased interest during recent years in the use of topical vehicles that may modify drug penetration into the skin. However, the complex structure of the skin and especially its uppermost layer, the stratum corneum, function as a rate limiting barrier for topical drug delivery. Various strategies have been employed to achieve the delivery of drugs into the skin. Among these strategies, vesicular carriers such as liposomes, ethosomes, transfersomes, and, more recently, transethosomes have been suggested to serve as efficient promoters of drug localization within the skin. Transethosomes contain phospholipids, surfactants, and a high percentage of ethanol. They have shown to enhance the skin penetration of lipophilic drugs. In this study, transethosomes have been developed, characterized, and loaded with a model lipophilic drug, fluvastatine. The in vitro pig skin penetration of fluvastatine from transethosome dispersion under occlusive and non-occlusive conditions have been determined quantitatively by using the tape stripping method. An ATR-FTIR spectroscopy has been used to study the interaction of transethosomes with the skin lipids. As a result, a topical transethosomal carrier which optimizes drug localization within the skin when applied under non-occlusive conditions has been developed.