Autoimmunity and allergies affect a large number of people across the globe. Current approaches to these diseases target cell types and pathways that drive disease, but these approaches are not cures and cannot differentiate between healthy cells and disease‐causing cells. New immunotherapies that induce potent and selective antigen‐specific tolerance is a transformative goal of emerging treatments for autoimmunity and serious allergies. These approaches offer the potential of halting—or even reversing—disease, without immunosuppressive side effects. However, translating successful induction of tolerance to patients is unsuccessful. Biomaterials offer strategies to direct and maximize immunological mechanisms of tolerance through unique capabilities such as codelivery of small molecules or signaling molecules, controlling signal density in key immune tissues, and targeting. While a growing body of work in this area demonstrates success in preclinical animal models, these therapies are only recently being evaluated in human trials. This review will highlight the most recent advances in the use of materials to achieve antigen‐specific tolerance and provide commentary on the current state of the clinical development of these technologies.