Since 1958, when HCL was first recognized as a new clinical, hematologic and pathological entity, great progress has been made through the contributions of numerous investigators: The hematopathology of the hairy cell and the organs involved by the disease have been well established. The early controversies concerning the cellular origin of the hairy cell has been clarified and is now recognized that the hairy cell of HCL is of B-lymphocyte lineage. The position of the hairy cell within the spectrum of B-cell chronic lymphoproliferative-disorders indicates that the CLL-lymphocyte is in an early stage and the hairy cell of HCL in a later stage in mature B-cell development. The hairy cell represents an activated B-CLL lymphocyte. The comparison of the immunophenotyping patterns of HCL and the other lymphoproliferative disorders is being clarified. Monoclonal antibodies raised against hairy cells or with restricted specificity for hairy cells, as well as other biological markets such as IL-2 and TNF, are being used for monitoring response to treatment and detecting minimal residual disease. In the last decade, major advances have been made in the treatment of HCL with the advent of interferon and the nucleosides. Our goal today is to achieve a complete response of prolonged or permanent duration. For this reason: Splenectomy, has only a few indications at present. After 10 years of experience with the interferons it is recognized that interferon induces a few complete responses and all patients eventually relapse. Currently the nucleosides: dCF and 2-CdA are the first line of treatment of HCL. Both drugs have acceptable toxicity and induce complete remissions in the majority of patients. However, longer periods of observation are needed to establish the duration of response and to document if any patients will attain a cure by the nucleosides. In the continuation of the progress in achieving our goals, we definitely need: better parameters for the evaluation of complete response and detection of minimal residual disease: to search for the characteristics for prediction of response to therapy; long-term randomized studies between dCF and 2-CdA as an initial therapy, as well as randomized treatment of relapsed patients to determine the incidence of reinduction or cross-resistance. Meanwhile the work has to continue with the development of newer strategies and of new drugs, if our goal of cure of HCL patients is to be attained.