Carsten Niemann, MD, PhD of Rigshospitalet, Copenhagen, Denmark gives an overview of his talk on the treatment of previously treated patients with chronic lymphocytic leukemia (CLL) held at the 2016 International Workshop of the German CLL Study Group (GCLLSG) in Cologne, Germany. Dr Niemann explains how the US and the developing European guidelines suggest, that all CLL patients who relapse, are in need of novel targeted agents. Dr Niemann challenges this view. It makes a difference if the first-line treatment was chemmoimmunotherapy or something else and also, not all patients are alike. For example, some patients may have long lasting responses and these baseline characteristics at the time of second-line treatment are important and influence the decision on what kind of next-line treatment should be given. Dr Niemann also addresses supportive care and the risk of infections.