Abstract Cladribine, a purine nucleoside analogue, is a safe and effective treatment for patients with hairy-cell leukaemia. It is administered at a dose of 0.09 mg/kg daily as a continuous intravenous infusion over 7 days. This chapter discusses the history, rationale, chemical structure and mechanism of action of cladribine. The indications for therapy and guidelines for clinical usage are reviewed. The response of hairy-cell leukaemia to cladribine, the acute and chronic complications and the risk for second malignancies are summarized. The chapter concludes with a section on salvage therapy.