Chronic B-cell malignancies are characterized by accumulation of transformed B cells of low proliferative index in lymphatic and extralymphatic tissues. Cytokines do not appear to play a role in the primary step of transformation. However, proliferation as well as inhibition of apoptosis of malignant B cells can readily be explained by cytokine effects. Clinical trials of interferons (IFN) and interleukin-2 alone or in combination have been performed in patients with hairy cell leukemia (HCL), CLL, and low- and intermediate-grade non-Hodgkin's lymphoma. While IFN alpha became standard therapy of HCL, responses in other entities were variable, ranging from 0 to 70% in selected populations. Combination of IFN and cytotoxic chemotherapy in general revealed no additional benefit as compared to chemotherapy alone. Perspectives for future clinical testing of cytokines in low-grade B-cell lymphomas are discussed.