Key Points Depressive symptoms are often but not always triggered by a loss, disappointment, or traumatic experience(s) and typically include irritability, low mood, demoralization, or a combination of these symptoms; they often also include fearfulness, poor concentration and/or school performance, low confidence, withdrawal from friends, somatic concerns, weight loss or gain, poor or excessive sleep, and impaired functioning, even in the absence of a diagnosable disorder.Depressive symptoms undisclosed to the family or clinician may be detectable by general psychosocial screening and/or specific depression screening—the latter recommended routinely by the US Preventive Services Task Force and Bright Futures for youths 12 years and older.Pediatric clinicians can meaningfully intervene, even in the absence of a diagnosis, through expressions of hope, empathy, and support to the youth and family; recognition and care of trauma-related symptoms; brief interventions derived from cognitive behavioral therapy (CBT); and referral for emergency mental health care if the youth is found to have either severe functional impairment or suicide risk.For youths diagnosed with major depressive disorder (MDD), pediatric clinicians can comanage care with a provider of CBT and either prescribe medication or monitor medication prescribed by a mental health specialist; evidence demonstrates that combined treatment with CBT and medication results in the largest rate of remission, although either modality alone can work at times if combined therapy is inaccessible or desired by families.