In this video, Alberto Orfao, MD, PhD, University of Salamanca, Salamanca, Spain, discusses measurable residual disease (MRD) monitoring in chronic lymphocytic leukemia (CLL) and clinical implications. First, Dr Orfao gives some background on the stability of B-cell clones in monoclonal B-cell lymphocytosis (MBL) and CLL, and how this relates to disease progression. Dr Orfao then discusses how MRD monitoring should be incorporated in CLL, and factors that should be considered, including age and quality of life of patients. To conclude, Dr Orfao explains the importance of monitoring MRD levels in short-term and long-term treatment, and how this can be used to better understand disease progression and the efficacy of second or third-line therapies. This interview took place during the 2nd ESH Translational Research Conference on Chronic Lymphocytic Leukemia (ESH CLL), 2022.