Advances in the understanding of the natural history and prognosis of chronic lymphocytic leukaemia (CLL) and the introduction of new drugs and strategies have renewed interest in the treatment of this disease. Clinical trials in patients stratified according to risk factors are useful to determine the efficacy of different treatments. These advances currently allow treatment of CLL patients to be decided on a more rational basis. Patients in early clinical stage (Binet A, Rai 0) with non-diffuse bone marrow histopathology, and low, stable blood lymphocyte levels have a long survival and should not be treated unless the disease progresses. On the contrary, patients with poor prognostic features, such as advanced clinical stage (Binet B, C; Rai III, IV), diffuse bone marrow infiltration or high and rapidly increasing blood lymphocyte levels have a median survival inferior to 5 years and should be treated. Chlorambucil is still the mainstay for treatment of CLL but new agents such as fludarabine and 2-chlorodeoxyadenosine offer great promise. These agents are already the treatment of choice for patients failing standard therapies and its role as front-line therapy is being investigated in randomized trials. Whatever the treatment used, however, cure is rarely achieved. A number of situations (e.g. autoimmune cytopenias, hypersplenism) merit special treatment approaches (e.g. corticosteroids, splenectomy). Bone marrow transplants, albeit experimental in CLL, warrant investigation in younger patients with poor prognosis.