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INTRODUCTION the BCL2 inhibitor venetoclax has dramatically changed the treatment of chronic lymphocytic leukemia (CLL) and has introduced the concept of time-limited therapy with targeted agents. AREAS COVERED This review discusses the mechanism of action of venetoclax, adverse effects, and the clinical data with this agent as identified by a selective search of clinical trials in the PubMed database. Venetoclax is FDA-approved with anti-CD20 monoclonal antibodies; however, research is ongoing evaluating its efficacy when given in combination with other agents such as the Bruton's Tyrosine Kinase (BTK) inhibitors. EXPERT OPINION Venetoclax-based therapy is an excellent treatment option for patients interested in time-limited therapy and can be offered in both the front-line and relapsed/refractory settings. Tumor lysis syndrome (TLS) risk evaluation, preventative measures, and strict monitoring should be conducted while these patients ramp up to target dose. Venetoclax-based therapies produce deep and durable responses with patients often achieving undetectable measurable residual disease (uMRD). This has led to the discussion of MRD-driven, finite-duration treatment approaches, although longer term data is still needed. While many patients eventually lose uMRD status, re-treatment with venetoclax remains an area of interest with promising results. Mechanisms of resistance to venetoclax are being elucidated, and research is ongoing.