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Background: The treatment landscape of chronic lymphocytic leukemia （CLL） has tremendously evolved in the last decades, thanks to the introduction of more effective therapies. Summary: Frontline therapy for patients with CLL includes chemoimmunotherapy （CIT） and pathway inhibitors （PIs） （i.e., bruton tyrosine kinase inhibitors and BCL2 inhibitors）; the latter has proved to be more effective than CIT mainly in patients with high-risk features （e.g., TP53 aberrations and unmutated IGHV） with acceptable toxicity. Combinations of PIs are playing the protagonist role as frontline therapy for CLL. Key Messages: In this article, the management of treatment-na?ve patients with CLL is discussed.
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