This commentary focuses on irritability, one subtype of emotion dysregulation. We review literature demonstrating that irritability is not a developmental phenotype of bipolar disorder, but is longitudinally associated with unipolar depression and anxiety and genetically associated with unipolar depression, anxiety, and attention-deficit hyperactivity disorder. We describe how irritability is amenable to translational research, in part because of the relevance of frustrative nonreward, a model developed in rodents, to human irritability. Last, we demonstrate how such research has suggested a novel exposure-based intervention for irritability.