John Gribben, MD, DSc, FRCPath, FRCP FMedSci, of Barts and The London School of Medicine and Dentistry, London, UK, chairs a discussion with Wyndham Wilson, MD, PhD, of the National Cancer Institute, Bethesda, MD, on highlights from the second day of the International Workshop on Non-Hodgkin Lymphoma (iwNHL) 2015 meeting. They discuss how improved understanding of B-cell biology may be used to inform treatment decisions, including targeting B-cell receptor signaling with ibrutinib for the treatment of patients with diffuse large B-cell lymphoma.