This article provides a comprehensive review of irritability in youth, integrating clinical and translational findings. Irritability, defined as proneness to anger that can reach impairing levels, is a common issue in youth, often co-occurring with conditions like ADHD, autism spectrum disorder (ASD), and mood and anxiety disorders. The review highlights the need for routine assessment of irritability using specific tools, noting that informant effects are prominent and vary by age and gender. Irritability is associated with impairment and increased risk of suicidality, independent of co-occurring diagnoses. Trajectories of irritability have been identified, with some beginning early in life, and are linked to future mental health issues. The article discusses genetic and environmental factors, the role of frustration tolerance, and the importance of cultural context. It also reviews measurement tools, epidemiological data, and the relationship between irritability and other psychiatric conditions. Treatment options, including parent management training and cognitive behavioral therapy, are discussed, along with the need for rigorous randomized controlled trials. Neuroimaging and genetic studies are reviewed, emphasizing the need for methodological advancements to enhance understanding and treatment of irritability. The article concludes with a call for future research to address gaps in knowledge and improve clinical practice.This article provides a comprehensive review of irritability in youth, integrating clinical and translational findings. Irritability, defined as proneness to anger that can reach impairing levels, is a common issue in youth, often co-occurring with conditions like ADHD, autism spectrum disorder (ASD), and mood and anxiety disorders. The review highlights the need for routine assessment of irritability using specific tools, noting that informant effects are prominent and vary by age and gender. Irritability is associated with impairment and increased risk of suicidality, independent of co-occurring diagnoses. Trajectories of irritability have been identified, with some beginning early in life, and are linked to future mental health issues. The article discusses genetic and environmental factors, the role of frustration tolerance, and the importance of cultural context. It also reviews measurement tools, epidemiological data, and the relationship between irritability and other psychiatric conditions. Treatment options, including parent management training and cognitive behavioral therapy, are discussed, along with the need for rigorous randomized controlled trials. Neuroimaging and genetic studies are reviewed, emphasizing the need for methodological advancements to enhance understanding and treatment of irritability. The article concludes with a call for future research to address gaps in knowledge and improve clinical practice.