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The treatment landscape of treatment-naive chronic lymphocytic leukemia (TN-CLL) is rapidly evolving. As more and more new drugs and combinations are becoming part of therapeutic armamentarium, it becomes highly pertinent to understand the evidence for each of the treatment options to select the right drug for the right patient. We summarize the recent data of the available frontline treatment options. The novel agents can overcome adverse biological attributes and provide long-term disease control. MRD may become a reliable surrogate for survival in the evaluation of future therapies. FCR still remains one of the best options in a young fit CLL with mutated IGVH. Long-term follow-up data of ibrutinib confirm its efficacy and safety in both high-risk and elderly TN-CLL patients. A combination of venetoclax with obinutuzumab has provided the hope of fixed-duration therapy and the potential for functional cure in TN-CLL. Several other trials testing the efficacy of other targeted agents and the optimal sequencing approaches are underway. Chemoimmunotherapy holds its ground as an effective treatment in the IGVH-mutated CLL. The targeted agents either singly or in combination have become standard of care in many subsets of TN-CLL.