Chronic lymphocytic leukemia (CLL) involves the proliferation of a clonal population of B cells within the bone marrow that classically spreads to the blood and lymphatic system. Central nervous system (CNS) manifestations of CLL occur rarely, and no gold standard treatment regimen has been designated to date. We report a case of CLL with CNS involvement in a 68-year-old woman who presented with a severe headache 4 years after initial diagnosis. She was started on ibrutinib, which failed to clear her CSF of malignancy. Venetoclax was then added, and this was successful in clearing her CSF. For its CNS penetration and efficacy in achieving CSF remission of CLL, we propose that venetoclax be considered as a treatment option for CLL meningitis.