ObjectiveResearch and clinical interest in irritability have been on the rise in recent years. Yet several questions remain about the status of irritability in psychiatry, including whether irritability can be differentiated from other symptoms, whether it forms a distinct disorder, and whether it is a meaningful predictor of clinical outcomes. In this article, we try to answer these questions by reviewing the evidence on how reliably irritability can be measured and its validity.MethodWe combine a narrative and systematic review and meta-analysis of studies. For the systematic review and meta-analysis, we searched studies in PubMed and Web of Science based on preselected criteria. A total of 163 articles were reviewed, and 24 were included.ResultsWe found that irritability forms a distinct dimension with substantial stability across time, and that it is specifically associated with depression and anxiety in longitudinal studies. Evidence from genetic studies reveals that irritability is moderately heritable, and its overlap with depression is explained mainly by genetic factors. Behavioral and neuroimaging studies show that youth with persistent irritability exhibit altered activations in the amygdala, striatum, and frontal regions compared with age-matched healthy volunteers. Most knowledge about the treatment of irritability is based on effects of treatment on related conditions or post hoc analyses of trial data.ConclusionWe identify a number of research priorities including innovative experimental designs and priorities for treatment studies, and conclude with recommendations for the assessment of irritability for researchers and clinicians.