Recently, chemical enhancers have been shown to possess the ability to deliver antigens and generate immune responses. This was achieved by designing formulations that possess the ability to enhance skin permeability as well as exhibit high adjuvanticity. The rational design of such multi-functional formulations from first principles requires in-depth knowledge of interactions between chemical enhancers and skin, which exist for a very limited pool of chemicals. Hence, combinatorial libraries of chemical mixtures were screened. Studies have shown that in a randomly selected population of chemical formulations, certain binary mixtures of chemicals are far more potent in permeabilizing the skin as compared to single chemicals (Karande et al. 2004) . In vaccination studies, a third chemical was added with the goal of enhancing the ability to offer adjuvanticity. The lead chemical formulations were tested in mice using the model antigen ovalbumin. The formulations that exhibited high permeation and adjuvanticity potential in in vitro screening also induced high IgG titers in mice (Karande et al. 2009 ). In another study, penetration enhancers and immunomodulators oleic acid and retinoic acid were used to enhance transcutaneous immunization with inactivated influenza virus across tape-stripped skin (Skountzou et al. 2006) . Pretreatment of mouse skin with oleic acid elicited increased levels of influenza virus-specific binding and neutralizing antibodies to levels equivalent to those induced by intranasal immunization with inactivated influenza virus. Oleic acid and retinoic acid treatments differentially affected the pattern of cytokine production upon stimulation with influenza viral antigen and provided enhanced protection.