New therapeutic agents such as proteins, peptides, and nucleic acid-based agents are being developed every year, making it vital to find a non-invasive route such as nasal or pulmonary for their administration. However, a major concern for some of these newly developed therapeutic agents is their poor absorption. Therefore, absorption enhancers have been investigated to address this major administration problem. This paper describes the basic concepts of transmucosal administration of drugs, and in particular the use of the pulmonary or nasal routes for administration of drugs with poor absorption. Strategies for the exploitation of absorption enhancers for the improvement of pulmonary or nasal administration are discussed, including use of surfactants, cyclodextrins, protease inhibitors, and tight junction modulators, as well as application of carriers such as liposomes and nanoparticles.