John Gribben, MD, DSc, FRCPath, FMed Sci from Bart’s Cancer Institute, London, UK provides his chronic lymphocytic leukemia (CLL) highlights from the 2016 American Society of Hematology (ASH) Annual Meeting, held in San Diego, CA. Prof. Gribben was interested by presentations demonstrating follow-up data from on-going clinical trials; for example, the 5-year follow-up presented by Susan O’Brien on ibrutinib vs. chemo-immunotherapy in CLL. Jennifer Woyach presented interesting data on the emergence of molecular mechanisms of resistance and a novel assay developed to monitor resistance in CLL patients receiving ibrutinib treatment. Also presented during ASH 2016 were data on clonal evaluation and sub-clones of CLL, raising the big question whether chemotherapy is accountable for the emergence of subclones and poorer response to secondary treatments in CLL patients. Finally, Prof. Gribben explains the concept of maintenance treatment using lenalidomide, which may be a promising approach for poorer risk CLL patients in the future.