Prof. Stephan Stilgenbauer from University of Ulm, Ulm, Germany, defines ultra high-risk CLL and comments on its implications for patients. He outlines the highlights from American Society of Clinical Oncology 2014 and EHA 2014 in CLL, addressing the latest data with ibrutinib from the RESONATE trial, and on resistance issues observed with ibrutinib. He also comments on the use of single versus combination agents in CLL.