Abstract: The present invention relates to polypeptides that are capable of binding to a specific epitope on the neonatal Fc receptor (FcRn). In particular, the present invention relates to novel and improved polypeptides comprising immunoglobulin single variable domains (ISVDs), such as heavy-chain single variable domains, that are capable of binding to a specific epitope on FcRn. The invention further relates to constructs, compounds, molecules or chemical entities that comprise at least one of these ISVDs binding to a specific epitope on FcRn. The present invention further relates to methods for producing such polypeptides as well as to uses of such polypeptides for diverse applications, including but not limited to the extension of the half-life in vivo of therapeutic compounds and/or the prevention and/or treatment of a disease and/or disorder, such as but not limited to a proliferative disease, an inflammatory disease, an infectious disease or an autoimmune disease.