Diagnostic and prognostic markers are necessary to help in patient diagnosis and the prediction of future clinical events or disease progression. As promising biomarkers of selected diseases, the free light chains (FLCs)κandλwere considered. Measurements of FLCs are currently used in routine diagnostics of, for example, multiple myeloma, and the usefulness of FLCs as biomarkers of monoclonal gammopathies is well understood. Therefore, this review focuses on the studies concerning FLCs as new potential biomarkers of other disorders in which an inflammatory background has been observed. We performed a bibliometric review of studies indexed in MEDLINE to assess the clinical significance of FLCs. Altered levels of FLCs were observed both in diseases strongly connected with inflammation such as viral infections, tick-borne diseases or rheumatic disorders, and disorders that are moderately associated with immune system reactions, e.g., multiple sclerosis, diabetes, cardiovascular disorders and cancers. Increased concentrations of FLCs appear to be a useful prognostic marker in patients with multiple sclerosis or tick-borne encephalitis. Intensive synthesis of FLCs may also reflect the production of specific antibodies against pathogens such as SARS-CoV-2. Moreover, abnormal FLC concentrations might predict the development of diabetic kidney disease in patients with type 2 diabetes. Markedly elevated levels are also associated with increased risk of hospitalization and death in patients with cardiovascular disorders. Additionally, FLCs have been found to be increased in rheumatic diseases and have been related to disease activity. Furthermore, it has been suggested that inhibition of FLCs would reduce the progression of tumorigenesis in breast cancer or colitis-associated colon carcinogenesis. In conclusion, abnormal levels ofκandλFLCs, as well as the ratio ofκ:λ, are usually the result of disturbances in the synthesis of immunoglobulins as an effect of overactive inflammatory reactions. Therefore, it seems thatκandλFLCs may be significant diagnostic and prognostic biomarkers of selected diseases. Moreover, the inhibition of FLCs appears to be a promising therapeutical target for the treatment of various disorders where inflammation plays an important role in the development or progression of the disease.