The global burden of stroke is of continual major importance for global health. The present report addresses some of the core principles that could make stroke prevention work. The prevention of stroke shares many common features with other non-communicable diseases (NCDs); stroke prevention should therefore be part of the joint actions on NCD led by the WHO and member states. Stroke prevention is an integral part of both the 2011 UN declaration on actions on NCDs and the UN Post-2015 Sustainable Developmental Goals. Stroke prevention requires an intersectoral approach, with important responsibilities on the part of governmental bodies, non-government organizations and the health sector as well as communities, industries and individuals. Although official development assistance will need to be provided for the lowest income countries, financing will need to be raised for most countries by reallocation of resources within the country. Stroke is a prototype NCD in that there is overwhelming scientific evidence that with actions taken to reduce risk factors, the risk of stroke can be substantially reduced. Prevention of stroke will also have beneficial effects on cognitive decline and dementia. As most strokes do not lead to death, stroke statistics should not only focus on mortality, but also on disability and quality of life. All preventive actions should start early in life and continue during the life cycle. Prevention of stroke is a complex medical and a political issue with many challenges. Upscaling of efforts to prevent stroke are urgently needed in all regions, and the opportunity to act is now.