Commercial sexual exploitation and sex trafficking of children and adolescents represent a severe form of child abuse and an important pediatric health concern. Youth who are commercially sexually exploited have a constellation of clinical risk factors and high rates of unmet physical and mental health needs, including conditions that directly result from their victimization. Common physical health needs among commercially sexually exploited children and adolescents include violence-related injuries, pregnancy, sexually transmitted infections, and other acute infections. Common mental health conditions include substance use disorders, post-traumatic stress disorder, depression and suicidality, and anxiety. The existing literature indicates that trauma-informed approaches to the care of commercially sexually exploited youth are recommended in all aspects of their health care delivery. Additionally, medical education that attunes providers to identify and appropriately respond to the unique needs of this highly vulnerable group of children and adolescents is needed. The available research on commercial sexual exploitation and sex trafficking of children and adolescents remains fairly limited, yet is expanding rapidly. Especially relevant to the field of pediatrics, future research to guide health professionals in how best to identify and care for commercially sexually exploited children and adolescents in the clinical setting signifies a key gap in the extant literature and an important opportunity for future study.