In the past 20 years, important progress has been made in the understanding of the natural history and prognosis of chronic lymphocytic leukaemia (CLL). Based on the notion that the clinical manifestations of CLL are due primarily to the progressive accumulation of lymphocytes over time, several prognostic factors have been identified. The prognostic value of parameters reflecting tumour burden (i.e. lymphadenopathy, splenomegaly, anaemia and/or thrombocytopenia due to bone marrow failure), first identified empirically, has been confirmed in multivariate analyses of large series of patients. Furthermore, clinical staging systems that group the most relevant of these factors have also been developed. Patients in early stage (Binet A; Rai 0) have a long survival which, in some cases, may match that of the general population. In contrast, patients with advanced stage (Binet C; Rai III or IV) have a median survival < 2 years. The major limitation of staging systems is that they do not give information about the likelihood of progression for patients in early stage. Nevertheless, haemoglobin level, blood lymphocyte count, lymphocyte doubling time and bone marrow infiltration pattern are useful to identify subsets of patients in early stage with different progression and survival rates, with the 'smouldering' form of the disease being identified fairly accurately. With all these advances, therapy in CLL can now be indicated on a more rational basis. However, further biological insight is needed to elucidate the mechanism accounting for the different forms of the disease.