In this VJHemOnc podcast, experts Barbara Eichhorst, MD, University Hospital Cologne, Cologne, Germany, Lydia Scarfò, MD, Vita-Salute San Raffaele University and IRCCS San Raffaele Scientific Institute, Milan, Italy, and Anna Schuh, MD, PhD, University of Oxford, Oxford, UK, provide insights into the latest updates to the ESMO clinical practice guidelines for chronic lymphocytic leukemia (CLL). They cover key topics such as diagnostic advancements, frontline treatment strategies based on IGHV mutational status, the role of double oral combinations, the importance of measurable residual disease (MRD)-guided treatment, and the debate between time-limited and continuous regimens.