Although the immune system has developed mechanisms to distinguish "self" from "non-self," the presence of autoimmune diseases demonstrates that these mechanisms can be bypassed. The posttranslational modification of self-antigens is one way in which "new" antigens are created for which immune tolerance does not exist. We review some of the posttranslationally modified self-antigens associated with autoimmune diseases, how they arise, and how they break immune tolerance.