In 2012, the World Health Assembly endorsed an important new health goal: to reduce avoidable mortality from non-communicable diseases (NCDs) by 25% by 2025 (the 25 by 25 goal). It remains a truth today that, despite global rhetoric and resolutions, chronic NCDs remain the least recognised group of conditions that threaten the future of human health and wellbeing. This article highlights the importance of prioritising non-communicable diseases and calls for global action to address them. It provides a history of previous Lancet series on non-communicable diseases (2010, 2007, 2005). It offers an overview of the current Lancet series on non-communicable diseases which focus on country actions (rather than merely global political or multilateral agency responses), inequalities, the harmful effects of the food and drink industries, access to essential medicines, and improving the responsiveness of health systems. The objective of the current series is to present the case for including NCDs as part of the post-2015 framework being developed now and over the next 2 years by governments and the UN system. That framework includes systems of accountability to monitor, review, and act on the commitments and promises made by all partners.