Chronic lymphocytic leukemia (CLL) cells are exquisitely dependent on the B-cell lymphoma (BCL)-2 anti-apoptotic protein for survival; venetoclax is a highly BCL-2-selective antagonist that spares platelets. In this phase I trial, it was combined with rituximab in 49 patients with relapsed or refractory CLL or small lymphocytic lymphoma, and the recommended phase II dose was found to be 400mg/day in this setting. Clinical tumor lysis syndrome occurred in two patients who started the dose ramp-up at 50mg/day and resulted in one death. The overall response rate was 86% and minimal residual disease (MRD) negativity was attained in 57%. A total of 25 patients (51%) achieved complete response, 20 of whom (80%) were MRD negative. Grade 1/2 upper respiratory infection, diarrhea, and nausea were very frequent, affecting 57%, 55%, and 51% of patients, respectively. Grade 3/4 neutropenia affected 53% of patients and febrile neutropenia affected 12%. A total of 14% and 16% of patients, respectively, had grade 3/4 anemia and thrombocytopenia. This Recommendation is of an article referenced in an F1000 Faculty Review also written by Prithviraj Bose and Varsha Gandhi.