Hairy cell leukemia (HCL), comprising 2% of all leukemias, is a chronic disorder characterized by mononuclear cells with prominent cytoplasmic projections. For years, patients with HCL underwent splenectomies and then interferon alpha for treatment, which provided high response rates but low percentages of complete remission. More recent treatments with 2-chlorodeoxyadenosine result in 85%-90% complete remission, minimal toxicity, and lower rates of relapse using a single course of therapy. A second course of therapy can be administered if HCL continues to be resistant or recurs. New research using anti-CD22 recombinant immunotoxin BL22 is proving successful. With these latest chemotherapy options, patients' prognoses are optimistic.