The advent of highly reliable noninvasive celiac diagnostic tests has transformed the field of celiac disease, from diagnosis, to evaluation of epidemiology, to clinical and translational research. Serologic tests in their modern forms are highly sensitive and specific for diagnosis, allowing for consideration of avoidance of diagnostic intestinal biopsy in some settings. On the other hand, as predictors of intestinal damage and for use in monitoring disease activity, currently available noninvasive tests have been disappointing. Serologic tests, while a measure of disease activity, do not correlate well with histology or symptomatology, and it is unclear if they predict long-term risk. Additionally, while the many clinically available tests have improved accessibility, they can have widely different cutoff levels and overall performance, making the comparison of levels in individual patients over time and across populations quite difficult. In the future, we can expect to see improvement in the currently available serologic tests including tissue transglutaminase and deamidated gliadin peptide with expansion of the dynamic range of the tests, and the celiac care community should push for a standardization of assays that would simplify research and patient care. Additionally, current serologic tests are measures of the adaptive immune response in celiac disease but do not directly measure intestinal inflammation. Promising work on intestinal fatty acid-binding protein and other assays which directly measure intestinal damage may complement traditional serologic tests and further improve our ability to noninvasively diagnose and monitor celiac disease. The coming years hold promise for the continuing evolution of serum-based tests in celiac disease with the possibility of substantial improvement of patient care and clinical research.