Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in Europe and North America, and mainly affects older individuals. It has a very variable course, with survival ranging from months to decades. Major progress has been made in the identification of molecular and cellular markers that may predict prognosis in CLL patients. However, these advances have raised new questions about the biology, prognosis and management of CLL. Available treatments generally induce remission, although nearly all patients relapse and CLL remains an incurable disease. Advances in molecular biology have enhanced our understanding of the pathophysiology of the disease and, together with the development of new therapeutic agents, have made CLL management more rational and more effective. This review describes the recent advances concerning the prediction of prognosis involving novel molecular genetic techniques and treatment of CLL patients suggesting an evidence-based approach according to individual risk factors.