Statins have been prescribed extensively for their cholesterol-lowering properties and efficacy in cardiovascular disease. However, compelling evidence now exists that statins also have extensive immunomodulatory properties that operate independently of lipid lowering. Consequently, much attention has been directed towards their potential as therapeutic agents for the treatment of autoimmune disease. Modulation of post-translational protein prenylation seems to be a key mechanism by which statins alter immune function. In this Review, the effect of statin therapy on immune function, and how this relates to the pathogenesis of autoimmune disease, is reviewed alongside current opinion of what the key biological targets of statins are.