Lymphoproliferative disorders can be characterized by a certain set of pathogenic events. These include the upregulation of anti-apoptotic pathways guided by the BCL-2 protein family, and signalling by tumor surface immunoglobulin B-cell receptors (BCR). In this video, recorded at the 23rd Congress of European Hematology Association (EHA) 2018, held in Stockholm, Sweden, Francesco Forconi, MD, DM, PhD, FRCPath, from the University of Southampton, Southampton, UK, speaks about targeting these pathways to treat chronic lymphocytic leukemia (CLL). BCR signalling can be modulated using a BTK inhibitor like ibrutinib or acalabrutinib, and BH3 mimetics can be used to block anti-apoptotic mechanisms. Dr Forconi also discusses how the conservation of pathogenic pathways in different lymphoproliferative diseases has allowed for these low toxicity, high efficacy treatments to be translated from CLL to other diseases like macroglobulinemia.