Free light chains are proteins produced by B lymphocytes during the process of antibody synthesis. Their production, as a reflection of B cell activation, can give insight into the activity of the adaptive immune system. In recent years, an automated immunoassay that provides quantitative measurement of free light chains in the serum has been developed. This assay has not only revolutionised the investigation of monoclonal light chain overproduction in plasma cell diseases, but has also allowed for the quantification of polyclonal free light chains in serum. The discovery of high levels of polyclonal free light chains in a number of inflammatory and auto-immune conditions has led to the examination of their value as a biomarker of disease activity. Research into their bio-activity has also highlighted their potential role in the pathogenesis of inflammatory disease, making them an attractive target for novel therapies.