Human trafficking has been increasingly recognized worldwide as a major public health problem. It is a crime based on exploitation of the most vulnerable and marginalized people of any community and is a violation of human rights. Children, especially immigrant and refugee children, are at risk of victimization and may experience considerable physical and mental health consequences. Adding these problems to pre-existing vulnerabilities and adversities makes human trafficking a complex health issue that needs to be addressed by a multidisciplinary team that includes health care providers. This article aims to provide an overview of human trafficking and the red flags that may alert the pediatrician to the possibility of exploitation, with a special focus on immigrant and refugee children. It describes a trauma-informed, rights-based approach and discusses ways in which pediatricians can contribute to a multidisciplinary response to human trafficking.[Pediatr Ann. 2020;49(5):e209–e214.]