Alan Skarbnik, MD, and Manni Mohyuddin, MBBS, discuss measurable residual disease (MRD) in blood cancers, highlighting controversies, implications of MRD negativity, harmonizing MRD thresholds, and testing MRD technology in trials. They explore the challenges in achieving and maintaining MRD negativity for long-term disease control, individualized approaches based on disease specifics, and the importance of overall survival benefits in chronic diseases like CLL.