The purine nucleoside analog - cladribine (2-chlorodeoxyadenosine, 2-CdA) is a cytotoxic agent with high activity in lymphoid and myeloid malignancies. It is also an effective drug in some autoimmune disorders. 2-CdA is usually administered intravenously in continuous or 2-hour infusion. Recently however, new formulation of this agent has been developed for subcutaneous and oral administration. 2-CdA is widely established as first line standard treatment for hairy cell leukemia. Moreover several clinical trials have demonstrated that this agent, used alone or in combination with other cytotoxic drugs, showed good efficacy and acceptable toxicity profile in the treatment of chronic lymphocytic leukemia, Waldenstrom macroglobulinemia, low-grade non-Hodgkins lymphoma and acute myeloid leukemia. Moreover, some studies indicate that 2-CdA has some activity in progressive multiple sclerosis and other autoimmune disorders including autoimmune hemolytic anemia, rheumatoid arthritis, systemic lupus erythematosus, psoriasis and in patients with refractory factor VIII inhibitors. This review article will summarize the results of recent clinical trials with 2- CdA in hematological malignancies, multiple sclerosis and other autoimmune diseases.