Cladribine is a deoxyadenosine analogue prodrug that preferentially depletes lymphocytes, key cells underlying multiple sclerosis (MS) pathogenesis. Cladribine tablets (Mavenclad®) represent the first short-course oral disease-modifying drug (DMD) for use in MS. The tablets, administered in two short courses 1 year apart, are indicated for the treatment of adults with highly active relapsing MS on the basis of data from pivotal clinical trials, including the phase 3 study CLARITY and its extension. A cumulative cladribine tablets dose of 3.5 mg/kg administered in this fashion in CLARITY reduced clinical relapse, disability progression and MRI-assessed disease activity and also improved some aspects of health-related quality of life (HR-QOL) versus placebo over 96 weeks in adults with relapsing-remitting MS (RRMS). Moreover, in the 96-week extension (plus 24 weeks' supplemental follow-up), no additional clinical benefit was gained from continuing versus discontinuing cladribine tablets after the first two annual courses of therapy, although MRI activity was more notable in a subset of cladribine tablet recipients who discontinued the drug. In post hoc analyses of CLARITY and/or a phase 2b trial, benefits of cladribine tablets were seen in patients with high disease activity (HDA) relapsing MS that were sometimes greater than in patients without HDA. Cladribine tablets have an acceptable tolerability profile and do not appear to be associated with an increased risk of overall infection or with an increased risk of malignancy (vs. matched reference populations). Active comparisons and longer-term follow-up would be beneficial, although current data indicate that for adults with highly active relapsing MS, cladribine tablets are an effective treatment option with the convenience of low-burden, short-course, oral administration.