The neonatal Fc receptor (FcRn) is functionally linked to the transport of immunoglobulin G (IgG) across various cellular barriers. It mediates the acquisition of humoral immunity in mammals through the transfer of IgG from mother to offspring, and it mediates the mucosal defense of the intestinal and respiratory tract in adults. In addition to mediating the transcytosis of IgG the FcRn is also involved in the regulation of the concentration and persistence of IgG in serum. The concentration of IgG in circulation is regulated by the FcRn present in the endothelial cells of the microvasculature. FcRn binds to IgG molecules that are internalized by fluid phase pinocytosis. The IgG molecules that bind to FcRn are salvaged from degradation and are recycled back into the circulation. In the absence of binding to FcRn the IgG undergoes degradation. This process maintains the constant level of IgG in serum. The role of FcRn as a homeostat of IgG is supported by the finding that the half life of IgG decreased in knock out mice lacking a functional FcRn. This review focuses on the role of FcRn in the homeostasis of IgG and the therapeutic implication of its function.