Summary Human proneness to anger, or irritability, has from the earliest writings on physical health represented a disturbance in physiological function and manifested itself as a disturbance of mood. Since antiquity, irritability has been associated with a range and variety of irascible verbal and physical behaviours. Yet, for the most part, the literature on irritability lies buried and forgotten. Our current conceptualization of irritability, a symptom present in a variety of mental and physical conditions, might be traced to the disease model of mental illness prevalent in medicine in the late 19th and early 20th centuries. Irritability, and not depression or anxiety, is frequently the primary presenting complaint in women with premenstrual, perinatal, and perimenopausal mood disturbances. Both the historical writings and contemporary research in particular research on female-specific mood disorders, suggest congruence with the notion of severe irritability as a distinct mood condition. This overview represents not an introduction but rather a resurrection of a longstanding and familiar, yet elusive phenomenon.