The functional activity of immunoglobulin free light chains in mast cell-dependent hypersensitivity-like responses implicates a potential role for these molecules in other immune disorders. Mast cell-bound immunoglobulin free light chains recognize antigen and induce mast cell activation and mediator release. Through this mechanism, immunoglobulin free light chains can contribute to the pathogenesis of e.g. contact hypersensitivity and non-atopic asthma. These findings shed new light on the potential role of immunoglobulin free light chains in autoimmune disorders, such as multiple sclerosis and rheumatoid arthritis. Immunoglobulin free light chain levels are increased in these disorders and correlate with disease activity. Further establishing the contribution of immunoglobulin free light chain-mediated mast cell activation to the pathogenesis of chronic inflammatory diseases may lead to novel therapeutic strategies in their treatment.