Exploitation and labor and sex trafficking of children and adolescents is a major public health problem in the United States and throughout the world. Significant numbers of US and non-US-born children and adolescents (including unaccompanied immigrant minors) are affected by this growing concern and may experience a range of serious physical and mental health problems associated with human trafficking and exploitation (T/E). Despite these considerations, there is limited information available for health care providers regarding the nature and scope of T/E and how providers may help recognize and protect children and adolescents. Knowledge of risk factors, recruitment practices, possible indicators of T/E, and common medical, mental, and emotional health problems experienced by affected individuals will assist health care providers in recognizing vulnerable children and adolescents and responding appropriately. A trauma-informed, rights-based, culturally sensitive approach helps providers identify and treat patients who have experienced or are at risk for T/E. As health care providers, educators, and leaders in child advocacy and development, pediatricians play an important role in addressing the public health issues faced by children and adolescents who experience exploitation and trafficking. Working across disciplines with professionals in the community, health care providers can offer evidence-based medical screening, treatment, and holistic services to individuals who have experienced T/E and assist vulnerable patients and families in recognizing signs of T/E.