The delivery of therapeutic proteins by noninvasive routes of administration has been a challenging goal, hence current modes of delivery generally require injections. However, we have recently shown that a naturally occurring receptor, the neonatal Fc receptor (FcRn) can be utilized to carry aerosolized therapeutic proteins conjugated to a portion of its respective ligand (Fc domain of immunoglobulin G) across epithelial cells of the lung to effectively deliver biologically active molecules to the bloodstream. First-generation dimeric Fc fusion molecules were successfully transported by the pulmonary route and biologic activity was demonstrated in both non-human primates and human volunteers. Continuing efforts to improve transport efficiency have led to the development of an alternate configuration of Fc fusion proteins with improved characteristics. These second generation Fc fusion molecules are monomeric with respect to the therapeutic protein and dimeric with respect to the Fc region, and have been termed Fc fusion 'monomers'. Several different Fc fusion monomers have demonstrated improved transport efficiency, achieving high bioavailabilities for pulmonary delivery in non-human primates. While the traditional dimeric Fc fusion molecule generally increases the half-life compared with the unconjugated effector molecule, the monomer configuration has been shown to result in an even greater extension of the circulating half-life, which improves pharmacokinetic parameters for protein therapeutics, whether administered by pulmonary delivery or injection. Finally, many of the Fc monomer fusions have enhanced biologic activity compared with the dimeric configuration. Because of these many advantages, the monomer configuration promises to be an enabling advance to achieve clinically relevant, noninvasive delivery with potentially less frequent administration regimens for a broad range of protein therapeutics. In addition, molecules that are comprised of heterodimeric subunits or multi-subunit complexes can also be constructed as Fc fusions that result in a molecule with enhanced pharmacokinetics and greater bioactivity. Several examples of novel Fc fusion proteins, both monomer and heterodimer are described herein.