 Abstract autoimmunity and allergies affect millions of people worldwide. Traditional treatments target specific cell types and pathways involved in the diseases, but they do not provide long-term solutions and can have adverse side effects. Immunotherapy approaches that induce potent and selective antigen-specific tolerance are promising alternatives with the potential to halt or reverse the diseases without immunosuppression. Materials such as biomaterials can be used to deliver small molecules or signaling molecules, control signal density in key immune organs and target specific areas of the body. Recently, these therapies have been successfully tested in animal models and are now being evaluated in human trials. Despite some progress, there is still much work to be done before these therapies can be widely adopted. This article was authored by Sean T. Carey, Christopher Bridgeman, and Christopher M. Jewell.