35 million people die annually of non-communicable diseases (NCDs), 80% of them in low- and middle-income countries — representing a marked epidemiological transition from infectious to chronic diseases and from richer to poorer countries. The total number of NCDs is projected to rise by 17% over the coming decade, absent significant interventions. The NCD epidemic poses unique governance challenges: the causes are multifactorial, the affected populations diffuse, and effective responses require sustained multi-sectorial cooperation. The authors propose a range of regulatory options available at the domestic level, including stricter food labeling laws, regulation of food advertisements, tax incentives for healthy lifestyle choices, changes to the built environment, and direct regulation of food and drink producers. Given the realities of globalization, such interventions require global cooperation. In 2011, the UN General Assembly held a High-level meeting on NCDs, setting a global target of a 25% reduction in premature mortality from NCDs by 2025. Yet concrete plans and resource commitments for reaching this goal are not yet in the offing, and the window is rapidly closing for achieving these targets through prevention — as opposed to treatment, which is more costly. Innovative global governance for health is urgently needed to engage private industry and civil society in the global response to the NCD crisis.