The genome sequence is an essential prerequisite for defining the complete gene catalogue of an organism, and it provides a framework for identifying and understanding the function of variants associated with phenotypic traits of interest. For wheat, these traits include disease resistance, crop yield improvement, protein content, quality factors and resistance to abiotic stressors such as drought or poor soils. This chapter reviews the challenges posed by the structure and composition of the wheat genome and how they are being addressed through genome sequencing strategies. It describes the sequencing approaches and resources that have been generated to date and provides some examples of how they are used. The chapter also discusses the road map of the International Wheat Genome Sequencing Consortium for the completion of a reference sequence that will meet the needs of breeders and researchers seeking to improve crop varieties and to understand the dynamic genome environment and complexity of the world’s most important crop.