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Hairy cell leukemia is relatively rare, chronic low grade B-cell leukemia. It is characterized morphologically by cells with abundant cytoplasm and “hair”-like projections that can be found within the peripheral blood, bone marrow or splenic pulp. Like many cancers, the treatment for hairy cell leukemia has evolved considerably in the last several years. In the mid 1980s, the acceptable treatment was splenectomy and later interferon therapy, which is quickly falling out of favor with the advent and acceptance of purine analog therapy. In addition, we now have several biologic agents that are coming into favor based on their improved success and favorable toxicity. In addition, several studies are currently looking into the efficacy of purine analogs in conjunction with biologic agents. Rituximab, alemtuzumab and recombinant immunotoxins are being studied with limited success in hairy cell leukemia. The use of kinase inhibition is also being studied at this time. Advances in understanding the biology of hairy cell leukemia could potentially increase more treatment options.