With the many new second generation therapies for chronic myeloid leukemia (CML), there is some debate as to which therapy should be used in the first-line setting, and indeed whether the existing standard of care, imatinib, is adequate. In this video, recorded at the 23rd Congress of the European Hematology Association (EHA) 2018, held in Stockholm, Sweden, Richard Clark, MA, MD, MRCP, FRCPath, of the Royal Liverpool University Hospital, Liverpool, UK, gives his opinion on this contentious topic. He says that while response is greater with novel therapies, toxicity is also increased relative to imatinib. He suggests that new prognostic markers should be developed to accurately determine which patients will respond sufficiently to imatinib, and which patients require more aggressive frontline treatment.