Non-communicable diseases (NCDs) now account for more than 36 million deaths each year; many of which are premature. Pacific Islanders are some of the worst afflicted by obesity and diabetes with prevalence of both diseases rising disproportionately faster in the Pacific region over the past three decades than in the rest of the world. A high burden of disease is also found among enclaves of Pacifican migrants in the USA, Australia, and New Zealand. Urgent action is needed to alleviate the high economic and personal costs now associated with NCDs in Pacific Islanders. In this article, we describe contributors to the temporal trends in obesity and diabetes, discuss the current burden of disease in the Pacific Islands and among migrant communities, and suggest priorities for future research in this area. Finally, we discuss challenges unique to intervention among Pacific Islanders and highlight promising opportunities to reduce the NCD burden.