Advances in the understanding of neonatal Fc receptor (FcRn) biology and function have demonstrated that this receptor, primarily identified for the transfer of passive immunity from mother infant, is involved in several biological and immunological processes. In fact, FcRn is responsible for the long half-life of IgG and albumin in the serum, by creating an intracellular protein reservoir, which is protected from lysosomal degradation and, importantly, trafficked across the cell. Such discovery has led researchers to hypothesize the role for this unique receptor in the controlled delivery of therapeutic agents. A great amount of FcRn-based strategies are already under extensive investigation, in which FcRn reveals to have profound impact on the biodistribution and half-life extension of therapeutic agents. This review summarizes the main findings on FcRn biology, function and distribution throughout different tissues, together with the main advances on the FcRn-based therapeutic opportunities and model systems, which indicate that this receptor is a potential target for therapeutic regimen modification.