Wheat has low levels of the micronutrients iron and zinc in the grain, which contributes to 2 billion people suffering from micronutrient deficiency globally. While wheat flour is commonly fortified during processing, an attractive and more sustainable solution is biofortification, which could improve micronutrient content in the human diet, without the sustainability issues and costs associated with conventional fortification. Although many studies have used quantitative trait loci mapping and genome-wide association to identify genetic loci to improve micronutrient contents, recent developments in genomics offer an opportunity to accelerate marker discovery and use gene-focussed approaches to engineer improved micronutrient content in wheat. The recent publication of a high-quality wheat genome sequence, alongside gene expression atlases, variation datasets and sequenced mutant populations, provides a foundation to identify genetic loci and genes controlling micronutrient content in wheat. We discuss how novel genomic resources can identify candidate genes for biofortification, integrating knowledge from other cereal crops, and how these genes can be tested using gene editing, transgenic and TILLING approaches. Finally, we highlight key challenges remaining to develop wheat cultivars with high levels of iron and zinc.