The immune system, through a complex interplay of highly specialized cells and a seemingly endless number of soluble mediators, works to ensure protection from the potentially harmful pathogens that we encounter in our lifetime. The development of the immune system is a compromise between the necessity to recognize foreign peptides in the context of self-molecules (MHC) and the need to be tolerant to all self-peptides. Despite the large number of mechanisms in place to ensure the removal or suppression of self-reactive lymphocytes, the system is not 100% effective, with the occasional result of autoimmunity. A number of autoimmune disorders occur together and a better understanding of the genetic basis underlying this association should lead to an enhanced ability to predict, diagnose, and develop therapies aimed at preventing and treating these diseases.