Jacqueline Barrientos, MD of Northwell Health Cancer Institute, Lake Success, NY gives an overview of chronic lymphocytic leukemia (CLL) therapies and sequencing of therapies at the 2016 American Society of Hematology (ASH) Annual Meeting, held in San Diego, CA. Dr Barrientos explains the importance of taking into account patient characteristics at the time of therapy; before therapy is started, it is important to check for TP53 mutation and 17p deletion as it affects the choice of therapy. For patients who do not tolerate ibrutinib, venetoclax is now available for patients with a 17p deletion or TP53 mutation; she also mention the use of idelalisib for this indication. For patients without these mutations, therapy choice depends on their characteristics and particularly their fitness. If they are fit, regimens such has fludarabine, cyclophosphamide, rituximab (FCR) should be considered. She further explains the complications associated with FCR therapy and explains the alternative, i.e. bendamustine-rituximab (BR). A trial that has finished accrual will compare FCR against ibrutinib in combination with rituximab and another trial will look at BR against ibrutinib in combination with rituximab or as monotherapy. She further explains the issues with targeted therapy, i.e. the question of discontinuation, and discusses the combinations of obinutuzumab with chlorambucil and ofatumumab with chlorambucil. She then outlines considerations behind sequencing therapies, including options for patients who relapse within the first three years and patients treated with tyrosine kinase inhibitors (TKIs). Further, she discusses data presented at ASH 2016 by Anthony Mato on venetoclax, ibrutinib and idelalisib and data on acalabrutinib and other new agents that are in the pipeline.