Growing evidence reflects the value of using an ecological, gender-affirming approach to TGD youth in all settings, but especially in primary care. Supportive acceptance from a known PPCP can facilitate medical and psychosocial supports that will enable TGD youth to live their authentic gender experience at home, at school, and in their community. • Based on strong recommendations B, C, and D, a pediatric gender-affirmative care model acknowledges an individual's unique gender experience within their developmental process. It naturally builds on the family-centered, strength-based focus of primary care pediatrics to foster positive development through open communication, empathy, and resiliency. • Based on strong recommendations B and C, transgender and gender-diverse (TGD) youth may present to the clinical setting with heightened distress as they go through the physical and emotional changes of puberty. TGD youth may not explicitly identify gender concerns but might instead exhibit high-risk behaviors and social disengagement (eg, school failure, social isolation, substance use, self-harm, disordered eating, high-risk sexual behaviors). • Based on strong recommendations C, D, and X, PPCPs play an essential role in identifying and normalizing gender diversity early so that family support and understanding can be established. This is achieved through routine gender screening and anticipatory guidance throughout childhood. • Based on strong recommendations C, D, and X, early identification provides increased engagement and support, timely targeted planning and treatment options, and an increased likelihood that the TGD youth's ongoing development will be congruent with their asserted gender identity. • Based on strong recommendations B, C, D, and X, there is growing understanding and research regarding best practice in gender care for children and adolescents. This knowledge base will continue to evolve, but current best practices support a gender-affirmative approach throughout childhood and adolescence. Approaches that force children to suppress rather than explore their authentic self, or that deny access to appropriate medical care and emotional supports, are detrimental to childhood health and well-being. Copyright © 2020 by the American Academy of Pediatrics. All rights reserved.