The best treatment protocol for hairy cell leukaemia (HCL) has not yet been defined. Different chemotherapies failed to demonstrate sustained benefit. Splenectomy certainly has been beneficial for many patients but has no effect on bone marrow infiltration by leukaemic cells. The introduction of Interferon-alpha (IFN-alpha), 2-deoxycoformycin (DCF) and 2-chlorodeoxyadenosine (2-CdA) in the therapy of HCL dramatically improved treatment options during the past decade. IFN-alpha does not have curative potential in HCL. 2-CdA seems to be more promising than DCF. Serum IL-2R level can be used as non invasive means to assess disease response to therapy. The predictive reliability of this test remains to be evaluated. The definition of complete remission remains open being greatly influenced by the sensitivity of the methods applied to detect residual disease. The role of the spleen as the reservoir of malignant cells can not be excluded in respect to the relapses of the disease.