Wheat provides 20% of calories and protein consumed by humans. Cereals represent 56% of world fertilizer nitrogen (N) consumption and the wheat crop accounts for 18.2% of global use. Nitrogen fertilizer represents a significant cost for the grower and also has environmental impacts through N leaching causing eutrophication of freshwater and marine ecosystems and N2O (a greenhouse gas) emission associated with denitrification by soil bacteria. The development of N-efficient cultivars will be of economic benefit to farmers and will help reduce environmental contamination associated with excessive inputs of N fertilizers. The physiological, metabolic and physico-chemical processes that may contribute to high N-use efficiency (NUE) and reduced N fertilizer inputs, while maintaining an acceptable yield, are reviewed and the prospects for application in breeding programs discussed. Promising traits for selection by breeders to increase NUE are identified, and their implications for breeding are discussed.