Hairy cell leukemia (HCL) is a chronic, low grade, non-Hodgkin lymphoma. This disease is relatively rare and represents 2% of all lymphomas. It is characterized by the accumulation of small, mature B-cell lymphoid cells with abundant cytoplasm and "hairy" projections that are found within the peripheral blood, bone marrow, and splenic red pulp. This accumulation results in significant splenomegaly and pancytopenia. Even though HCL is not curable, prognosis for classic HCL is relatively better. Therapeutic options for HCL include: watchful waiting, splenectomy, purine analogs, and more novel immunotherapies and targeted kinase inhibitors. The majority of patients do not require therapy immediately upon diagnosis. Indications for treatment are symptomatic disease with debilitating fatigue, massive splenomegaly leading to abdominal pain, weight loss secondary to early satiety and bone marrow failure. Most patients show excellent long-term response to treatment with a single-agent purine analog. The increasing number of patients, who either relapse or become refractory to purine analog therapy, led to more studies for a better understanding of the HCL pathobiology and more effective treatment options.