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Other patients present with symptomatic advanced disease that rapidly progresses and requires therapy. For these patients, chemotherapy is the mainstay of treatment and has undergone significant evolution in the past few decades. From alkylating agents to purine analogs, response rates have greatly improved with new chemotherapy regimens. The development of chemoimmunotherapy regimens has also transformed the treatment of CLL. This article will review front-line treatment options for CLL and discuss the updated National Comprehensive Cancer Network guidelines. 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