Transgender and gender-diverse (TGD) youth may present to the emergency department with a range of medical problems and health concerns. Some of these may be directly related to their gender identity, but the vast majority are not. While gender diversity is not considered a mental illness, TGD youth are at increased risk for suicide, anxiety, depression, and other psychological conditions, as well as family rejection, homelessness, food insecurity, and poverty. Lack of knowledge and cultural competency among emergency clinicians can create a barrier to effective care. This issue will review relevant terminology, epidemiology, and clinical best practices. It will help emergency clinicians understand common gender-affirming practices and recognize possible complications.