The development of safe and effective antigen-specific therapies is needed to treat patients with autoimmune diseases. These therapies must allow for the specific tolerization of self-reactive immune cells without altering host immunity to infectious insults. Experimental models and clinical trials for the treatment of autoimmune disease have identified putative mechanisms by which antigen-specific therapies induce tolerance. Although advances have been made in the development of efficient antigen-specific therapies, translating these therapies from bench to bedside has remained difficult. Here, we discuss the recent advances in our understanding of antigen-specific therapies for the treatment of autoimmune diseases.