In the 1950s Yalow and Berson developed a radioimmunoassay for insulin. It was the first case of immunoassay used for diagnostics, measuring glucose levels in diabetic patients. Later, Rosalyn Yalow received a Nobel Prize for this effort. In the 1970s Van Weeman and Schuurs replaced the radiolabel with enzyme labels. This reduced the hazard from radiation, and the turnover of substrate by the enzyme resulted in an amplification of the signal. With radioimmunoassay (RIA) a single binding event was detected by a single radioactive molecule, whereas a single binding event by an enzyme-labeled ligand resulted in increasing color formation as the enzyme turns over substrate. This conversion to enzyme labels also allowed more laboratories to utilize the method since the use of radiolabels often excluded laboratories because of regulatory barriers. Enzyme-linked immunosorbent assays (ELISAs) were also reported to have faster reaction times, greater specificity for the target molecule, and longer shelf lives compared to RIAs. Accompanying improvements to labels, efforts continue to improve the primary component of the immunoassay, the antibody. Polyclonal antibodies derived from immunizing mammals, primarily rabbits, sheep, goats, and donkey, are a standard reagent. However, the quality of the antibody may not be consistent because of animal to animal variability. In the 1980s, Köhler and Milstein developed a technique that fused antibody-producing B cells to a myeloma cell line. After fusion, an immortal monoclonal cell line producing a single antibody of interest is discovered though screening and results in a cell line that can continuously produce a well-defined reagent. This opened additional doors to commercialization of immunoassays. Recombinant technology has led to the development of antibody molecules expressed in E. coli and the discovery that fragments of the whole antibody molecule retain binding characteristics. Camelid antibodies have been found that have a different morphology consisting of a similar constant region, but the binding portion consists of only the variable heavy chain. This binding portion is 1/10th the size of the classical antibodywhile retaining high binding affinity and additional properties of thermal and chaotropic stability. Their small size makes them easier to clone and express and modify Published in the topical collection Immunoanalysis for Environmental Monitoring and Human Health with guest editors Shirley J. Gee, Ivan R. Kennedy, Alice Lee, Hideo Ohkawa, Tippawan Prapamontol, and Ting Xu.