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This chapter reviews the mechanism of action of cladribine, summarizes data from clinical trials in patients with multiple sclerosis (MS), and provides guidance on the management of these patients in clinical practice. The study of parenteral cladribine showed encouraging results, which lead to the development of an oral tablet formulation. Cladribine is rapidly absorbed with Cmax within 30- 50 minutes after oral administration. CLARITY, a 96-week, placebo-controlled Phase 3 study of cladribine tablets as an annual short-course oral monotherapy in RRMS, was recently completed and the principal results published. Benefit of doses of cladribine over placebo was demonstrated for a variety of clinical and imaging end-points. The most common adverse events in the patients were lymphopenia, headache, nasopharyngitis, and upper respiratory tract infections (URTI). The outcomes observed during the CLARITY study were associated with a reduced consumption of health care resources and a decreased need for medical and societal support.