In this roundtable discussion, chaired by Paolo Ghia, MD, PhD, Università Vita-Salute San Raffaele, Milan, Italy; Susan O’Brien, MD, University of California Irvine, Irvine, CA; Lydia Scarfò, MD, Università Vita-Salute San Raffaele, Milano, Italy and Othman Al-Sawaf, MD, University Hospital of Cologne, Cologne, Germany, review the most exciting updates in chronic lymphocytic leukemia (CLL) from the 2021 European Hematology Association (EHA) and International Conference on Malignant Lymphoma (ICML) meetings, including the latest data from the RESONATE-2, CLL14, MURANO and ELEVATE-RR trials, as well as talking on second-generation BTKs and fixed-duration therapy.