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Chronic lymphocytic leukemia (CLL) is the most diagnosed leukemia in the Western world, accounting for approximately 25% of all new leukemia diagnoses. In recent years, remarkable progress has been made in our understanding of both the pathophysiology and genetics of CLL. While the disease generally affects older adults and initially follows an indolent course, cytogenetic and molecular profiling have helped to predict clinical outcomes. Greater prognostication, alongside the development of an increasing armamentarium of novel targeted therapies, has enabled us to provide more personalized management options for patients.