Nicole Lamanna, MD, from Columbia University Medical Centre, New York, NY, provides an overview from the session on ‘Progression/Evolution of CLL: Mechanisms and Therapies’, which she co-chaired with Christopher Vakoc during the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2017 held in New York, NY. The session included presentations by leading chronic lymphocytic leukemia (CLL) experts, Dan Landau, Lesley Ann Sutton, Gianluca Gaidano and John C. Byrd, and focused on the development of clonal and subclonal mutations in CLL. Dr Lamanna describes how mutational evolution remains a significant challenge in the treatment of CLL, especially in the relapsed/refractory setting. As treatments move away from traditional chemotherapy and immunotherapy, there is interest in how this will affect the evolution of mutations over time. Dr Lamanna describes the benefits to being able to sequentially monitor patients’ mutations throughout their treatment and to track mutation evolution, with the aim of devising more effective therapy plans. Dr Lamanna also details the discussions on Richter’s transformation syndrome, a challenging and life-threatening condition for patients with CLL.