Alemtuzumab is a humanized monoclonal antibody that causes prolonged lymphopenia. In a recent Phase III trial, alemtuzumab was shown to reduce both the annualized relapse rate and the rate of sustained accumulation of disability by over 70% when compared with IFN-β1a. However, the drug is associated with thyroid autoimmunity in approximately a third of treated patients, as well as other secondary autoimmune conditions in smaller numbers. Secondary autoimmunity typically arises during reconstitution of the lymphocyte repertoire. Individuals with high baseline circulating levels of IL-21 are at highest risk of developing autoimmunity following treatment with alemtuzumab.