The standards of laboratory performance of the World Anti-Doping Agency (WADA)-accredited laboratories are defined in the WADA International Standard for Laboratories and its associated Technical Documents. These sets of rules aim to harmonize the production of valid laboratory test results and evidentiary data as well as the reporting of laboratory analytical findings. The determination of anti-doping rule violations in sport made on the basis of analytical quantitative confirmatory analyses for the presence of prohibited threshold substances, in particular, requires the application of specific compliance decision rules, which are established in the WADA Technical Document on Decision Limits. In this article, the use of measurement uncertainty information in the establishment of compliance Decision Limits and in evaluating the performance of a laboratory's quantitative analytical procedures over time and in relation to other laboratories through WADA's External Quality Assessment Scheme program is reviewed and discussed. Furthermore, a perspective is provided on the emerging challenges associated with the harmonization of the quantitative measurement of large-molecular weight biomolecules.