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Irritability is a common and impairing clinical presentation in children and adolescents. Despite its significant public health impact, irritability remains an elusive construct. Chronic and severe irritability is the primary symptom of the new DSM-5 diagnosis, disruptive mood dysregulation disorder (DMDD). However, empirical and clinical approaches to irritability are in their relative infancy, and questions regarding the validity of the DMDD diagnosis have been raised. Moreover, irritability is a trait distributed continuously in youth, thereby fitting within the National Institute of Mental Health Research Domain Criteria initiative. Thus, there are opportunities for scientific review and integration. Accordingly, the goals of this review include (a) clarifying the definitions of irritability, incorporating clinical and translational animal work; (b) reviewing the historical context surrounding the study of irritability; (c) reviewing the prevalence …