Climate change may be the greatest health threat of the twenty-first century, impacting lives both directly and indirectly, through undermining the environmental and social determinants of health. Rapid action to decarbonize economies and build resilience is justified on health, human rights, environmental and economic grounds. While the necessary health response is wide ranging, it can largely be encapsulated within three grand challenges: (i) promote actions that both reduce carbon emissions and improve health; (ii) build better, more climate-resilient and low-carbon health systems; and (iii) implement public health measures to protect from the range of climate risks to health. The health community can make a unique and powerful contribution, applying its trusted voice to climate leadership and advocacy, providing evidence for action, taking responsibility for climate resilience and decarbonization of healthcare systems, and guiding other sectors whose actions impact substantially on health, carbon emissions and climate resilience.