Drug induced autoimmune syndromes have been recognized for many years. The classical presentation is that of drug-induced lupus, a generally milder version of the idiopathic disorder that is associated with production of antihistone antibodies. This pattern is now changing, in part due to the many new drugs that have been introduced into clinical practice for treatment of autoimmune diseases, including both conventional pharmaceuticals and biologicals. The number and complexity of drug-induced autoimmune syndromes has increased, and many are now associated with autoantibodies that have been classically defined as limited to idiopathic disease states. Furthermore, some of these drug-induced syndromes have life-threatening complications, so that recognition of drug-induced disease has become more difficult at a time when it is more urgent to establish a correct diagnosis. Many reports are limited to case descriptions, and few controlled investigations have been carried out. Nevertheless, it is possible to derive an approach to considering possible mechanisms by which these processes may take place. This chapter will consider these proposed mechanisms, using some of the implicated drugs to illustrate possible pathogenetic pathways.