The opinions about the pathogenesis and prognostic factors of chronic lymphocytic leukemia (CLL) have undergone significant changes over the past decade and a variety of new prognostic factors have been discovered (ZAP-70; ATM; cytogenetic, molecular genetic and functional analysis of p53; a mutational status of IgVH; microRNA). On the other hand, however, indication for the start of therapy continues to be based on the conventional hematological and clinical findings, while a range of new and effective therapeutic procedures is now used in the CLL therapy. The exact current role of the new prognostic markers of CLL therefore remains undefined. This review focuses on the most recent advances in the diagnostic and prognostic examination of patients with CLL, with particular emphasis on their implications in clinical management. Risk stratification using biological prognostic markers can improve current patient care and direct future clinical research.