Children and adolescents with serious illness or medical complexity are often referred to highly specialized children's hospitals that offer experimental interventions, novel management, or treatments that cannot be provided at local health care centers. Referral to a geographically distant, highly specialized health center presents new complexity, with a distinct set of ethical issues, for patients, families, and clinicians. We describe ethical considerations that occur at the initiation of referral, during the process of referral, and after a referral for pediatric patients receiving hospital-based care. Using illustrative cases, we highlight salient themes surrounding these challenges that span many tenets of pediatric bioethics, including beneficence (ie, weighing benefits against harms), imposing values to impact shared decision-making, and justice (ie, lack of standardization in processes creating risk for discrimination). Pediatric clinicians and ethicists must be aware of the potential challenges arising in referring and transferring patients for higher levels of specialized intervention and treatment. When referral is indicated, institutions should facilitate collaborative care as much as possible by sharing information early, frequently, transparently, and in a standardized manner.