Anna Schuh, MD, PhD, from the University of Oxford, Oxford, UK gives an overview of her talk ‘How I manage difficult problems in CLL’ at the 2017 British Society for Haematology (BSH) Annual Scientific Meeting in Brighton, UK. Chemoimmunotherapy is a common treatment for chronic lymphocytic leukemia (CLL), however, some patients are not fit for chemotherapy. She describes a case where the patient presented with pancytopenia and a TP53 abnormality, that was treated with ibrutinib. Some patients, however relapse from ibrutinib therapy, for multiple reasons. These patients can be treated with more novel agents, such as venetoclax. The role of transplantation in treating CLL discussed, as well as the role of idelalisib and rituximab and the prevention of infection related side effects. This video has been supported by Napp Pharmaceuticals Ltd through an unrestricted educational grant to Magdalen Medical Publishing.