Human trafficking is a global problem taking many forms, including sex and labor exploitation. Trafficking victims can be any age, although most trafficking begins when victims are adolescents. Many trafficking victims have contact with health-care providers across various health-care contexts, both for emergency and routine care. We propose 4 specific areas where medical informatics can assist with combatting trafficking: screening, clinical decision support, community-facing tools, and analytics that are both descriptive and predictive. Efforts to implement health information technology interventions focused on trafficking must be carefully integrated into existing clinical work and connected to community resources to move beyond identification to provide assistance and to support trauma-informed care. We lay forth a research and implementation agenda to integrate human trafficking identification and intervention into routine clinical practice, supported by health information technology. A sociotechnical systems approach is recommended to ensure interventions address the complex issues involved in assisting victims of human trafficking.