Transgender people face alarmingly high rates of verbal harassment and physical violence, including at home and at school. Transgender youths face significant mental health issues as a consequence, including depression and suicidality, anxiety, body image distortion, substance abuse, and post-traumatic stress disorder. Part 3 of this first-of-its-kind 3-part series helps show how pediatric primary care providers (PPCPs) are uniquely situated to screen, identify, and care for transgender and gender-diverse youths. As children and adolescents become increasingly aware of gender diversity, PPCPs should be attentive to physical and emotional cues that point to gender-related distress. Early identification of distress in transgender patients, supported exploration of identity, and affirmation helps foster healthy growth and development in a particularly vulnerable population. It also leads to positive long-term health outcomes, including decreased morbidity and mortality.