Hairy cell leukemia is a malignancy with a variable course that can be relatively indolent or rapidly fatal. Alterations in the immune system are responsible for much of the morbidity and mortality from hairy cell leukemia. More than 60% of patients die from infection, and infections are both pyogenic and nonpyogenic. Many patients have transfusion requirements, and bleeding complications can also occur. Treatment strategies for hairy cell leukemia have evolved and are being modified as more is learned about the disease. Splenectomy is the initial treatment when patients become symptomatic, and if the disease progresses after splenectomy, chlorambucil offers good control in many patients. Radiation can be used for local palliation, as when complications such as bulky adenopathy or bone lesions occur. Initial studies using interferon in the treatment of hairy cell leukemia look encouraging, but more investigation is necessary before the role of interferon in treatment of hairy cell leukemia is determined.