Adverse drug reactions (ADRs) are commonplace and occur when a drug binds to its intended pharmacological target (Type A ADR) or an unintended target (Type B ADR). Immunologically mediated Type B ADRs, such as drug hypersensitivity syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS), and Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN), can be severe and result in a diverse set of clinical manifestations that include fever and rash as well as multiple organ failure (liver, kidney, lungs, and/or heart) in the case of drug hypersensitivity syndrome. There is increasing evidence that specific HLA alleles influence the risk of drug reactions. Several features of T cell–mediated ADRs are strikingly similar to those displayed by autoimmune diseases like type I diabetes, such as strong HLA association, organ-specific adaptive immune responses, viral involvement, and activation of innate immunity. There is a need to better predict patient populations at risk for developing immunologically mediated Type B ADRs. Since methods to predict type 1 diabetes using genetic and immunological biomarkers have been developed to a high level of accuracy (predicting 100% of individuals likely to progress), new research strategies based on these methods may also improve the ability to predict drug hypersensitivity.