Barbara Eichhorst, MD, of the University Hospital Cologne, Cologne, Germany, gives an overview of the mechanisms of drug resistance in chronic lymphocytic leukemia (CLL), as well as explaining how they can be predicted. Studies of resistance to Bruton’s tyrosine kinase (BTK) inhibitors has given a great deal of insight into resistance, enabling the development of second-generation targeted therapies. This interview took place at the 19th International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Biennial Meeting, held virtually in 2021.