Serial quantification of BCR-ABL1 mRNA levels is a sensitive and specific measure of response to therapy in patients with chronic myeloid leukemia and is used to define time-related clinical milestones as well as eligibility for stopping treatment. To improve the comparability of molecular monitoring results between centers, an international scale (IS) for BCR-ABL1 measurement has been implemented by testing laboratories worldwide, either by the derivation of laboratory-specific conversion factors or by using kits and reagents calibrated to the First World Health Organization International Genetic Reference Panel for quantitation of BCR-ABL1 mRNA. More recent attention has focused on defining deep molecular response (DMR) within the context of the IS and pushing the limit of detection of the test. While there has been substantial progress, accurate and sensitive BCR-ABL1 measurement remains technically challenging and standardization is an ongoing process.