Emerging infectious diseases place a substantial burden on human and animal health and well-being. Trends toward rapid environmental change, combined with human population growth, global trade and travel suggest that a preventive approach is essential for emerging infectious diseases likely to face society in the 21st century. To meet this challenge, One Health initiatives are being implemented to improve global capacity to recognize pandemic threats and respond more efficiently to outbreaks. The Emerging Pandemic Threats (PREDICT) program uses the One Health approach to integrate surveillance of potential disease threats at high-risk human-animal interfaces with risk characterization in many of the world’s most resource-limited settings.