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Purpose of Review: This review describes some of the unique challenges faced by the US-Affiliated Pacific Islands (USAPIs) in addressing diabetes prevention and care and presents innovative population-level strategies that have been employed to address them., Recent Findings: Challenges include an unhealthy food environment and a strained health care infrastructure, both compounded by geography. Innovations in addressing these challenges include attempts to modify the food environment, a focus on early life prevention, and task shifting among the health workforce. Many of the successful interventions share a focus on culture, community, and capacity building. Although the USAPIs are uniquely challenged by environmental, structural, and health system barriers, there have been a number of innovative and successful strategies employed that highlight the resilience of these island nations in addressing their current disease burden when provided with the opportunity and resources to do so. Health policies to protect, support, and promote diabetes prevention and care are essential and may be informed by the interventions described.