Humanity is facing its greatest challenge. To produce 70% more food by 2050 without destroying the environment means doing much more with less. Partly due to the abundant food and record-low food prices achieved by the Green Revolution, overseas development assistance for agriculture dropped from over $20 billion in the 1980s to as little as $3 billion in 2006. Stagnation in the yields of major crops such as rice, wheat and maize followed, and the status quo finally crumbled with the food prices and price spikes of 2008, 2010 and 2011. Today large segments of the global population are threatened by the depletion or degradation of natural resources. Making a bad situation worse, climate change further threatens agriculture by increasing the risk of droughts and floods, affecting temperatures and crop growing seasons and altering the distribution of pests and diseases. Agriculture holds enormous potential to reduce poverty in the developing world, strengthen the sustainability of our global food system, and rebuild and revitalise fragile communities so they can move from dependency to self-sufficiency. A holistic approach is now needed to take scientific innovations and move them along the chain into farmers’ hands and people’s stomachs. No one organisation can achieve that alone. This paper highlights how science has helped in the past, and outlines what it is going to take to boost agriculture in the future. Science is and always will be the backbone of CGIAR work, but now CGIAR is geared up for ‘science plus’. CGIAR is aggregating resources and disciplines as it works side by side with partners to reduce rural poverty, improve food security, nutrition and health while sustainably managing natural resources.