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Chronic lymphocytic leukemia (CLL) is the most common hematological malignancy in western countries. It is characterized by the accumulation of monoclonal CD5+ B-lymphocytes in blood, bone marrow, and lymphoid organs, due to an imbalance between proliferation and cell death. It is a complex disease that remains misunderstood. This book, therefore describes globally this very common but extremely complex type of leukemia. Throughout this book the principal biological hallmarks of B-cells are compared with the principal features of CLL-leukemic B-cells. Additionally the current CLL epidemiology is indicated and the most common methods of diagnosis are discussed. Moreover, the principal prognostic factors of CLL are described, passing from a medical point of view to a biological description. The major characteristics conferring apoptotic avoidance of CLL cells and proliferation factors are detailed, such as the principal models for its in vitro and in vivo study. Finally, the leading conventional treatments and new therapeutic strategies against CLL are listed with their principal biological targets.