BTK inhibitors have been important game changers in the management of B-cell lymphoma in general and B-CLL and small lymphocytic lymphoma in particular. Federico Pea, MD, University of Bologna, Italy, discussed differences between the irreversible BTK inhibitors ibrutinib, acalabrutinib and zanubrutinib. The second-generation drugs acalabrutinib and zanubrutinib demonstrated higher kinase selectivity than the first-in-class agent ibrutinib, which implies an improved efficacy-toxicity ratio.