Clinical studies involving the use of free light chain (FLC) immunoassays have been published in scientific journals since the 1960s. A variety of assay formats have been described including radioimmunoassay, enzyme immunoassay (EIA), radial immunodiffusion, turbidimetry and nephelometry; and some have been claimed to be specific for the measurement of FLCs in serum . However, it is only since Freelite FLC assays (Binding Site, UK) became commercially available that serum FLC (sFLC) measurement has come to be an integral part of routine clinical practice for the diagnosis and management of monoclonal gammopathies. Indeed, sFLC analysis is now included in various national and international guidelines (Chapter 25). In some countries, products intended for measurement of FLCs are commercially available from other manufacturers. This chapter provides an overview of the assays available, discusses the relative merits of monoclonal versus polyclonal antisera and presents data from the various published comparison studies.