Quantification of intact serum immunoglobulins has proven useful in the evaluation of patients with suspected immunodeficiency disorders, lymphocyte and plasma cell neoplastic diseases, allergic conditions, and some chronic inflammatory and autoimmune disorders. Since the advent of quantitative immunoglobulin assays nearly 50 years ago (1), increasingly robust analytical methods have been developed. The armamentarium of intact immunoglobulin assays was first substantively expanded by the development of immunoglobulin light-chain measurements in which the light chains are bound to heavy chains (intact immunoglobulins). The last decade has seen the development of both free (unbound) immunoglobulin light-chain assays and heavy/light-chain (HLC) or junctional epitope assays, the latter of which allows for individual measurements of IgGκ, IgGλ, IgAκ, IgAλ, IgMκ, and IgMλ (2, 3). Despite these advances in immunoglobulin and light-chain quantification methods, there remain technical complexities that can influence accuracy and, in turn, proper clinical application. Equally important, even with robust assays, is the need for thorough understanding of the clinical indications for, and limitations to, immunoglobulin and related measurements.