The bioavailability of drugs is often severely limited due to the presence of biological barriers in the form of epithelial tight junctions, efflux proteins and enzymatic degradation. Physicochemical properties, such as lipophilicity, molecular weight, charge, etc., also play key roles in determining the permeation properties of drug candidates. As a result, many potential drug candidates may be dropped from the initial screening portfolio. Prodrug derivatization targeting transporters and receptors expressed on mammalian cells holds tremendous potential. Enhanced cellular delivery can significantly improve drug absorption. Such approaches of drug targeting and delivery have been the subject of intense research. Various prodrugs have been designed that demonstrate enhanced bioavailability and tissue specificity. This approach is equally applicable to human and veterinary pharmaceuticals since most of the transporters and receptors expressed by human tissues are also expressed in animals. This review highlights studies conducted on the use of transporters and receptors in an effort to improve drug bioavailability and to develop targeted drug delivery systems.