The current management of B-chronic lymphocytic leukemia (CLL) is no longer straightforward for the practicing hematologist. Rapid advances in diagnostic precision, methods of predicting prognosis, understanding of natural history of CLL, recognition of clinical complications, clarification of the quality of life (QOL) issues facing the CLL patient, and the exciting array of novel treatment approaches have made the care of the CLL patient more demanding. This review is focused on summarizing these advances in order to provide a framework for integrating this knowledge into routine hematologic practice.