Wheat is the largest produced grain crop world-wide and has been extensively studied for a wide range of agronomic traits located across the genome. Its large chromosomes and the capacity of the polyploid genome to tolerate the addition or loss of chromosomes facilitated a fast progress in early wheat genetics using cytogenetic techniques. However, these same characteristics have limited the progress in genomic studies that have been focused on diploid model species with smaller genomes such as rice and Arabidopsis. These model systems are seen as a launching pad for comparative genomic strategies to tackle the challenges associated with the larger genomes of other plants such as wheat. The strengths and limitations of comparative genomic approaches to study the wheat genome are presented in this review. Structural genomic studies in wheat started by the development of large DNA insert libraries (BAC libraries) for the progenitor A and D genomes using diploid species and for the B genome using tetraploid wheat. Sequencing of the first wheat BAC clones has confirmed cytogenetic results indicating the presence of portions of the wheat genome that contain high density gene regions approximating that of the model species. These high-density gene regions also exhibited higher-than-average rates of genetic to physical distances. Functional genomic approaches, focused on the expressed portion of the wheat genome, have recently led to an exponential growth of expressed sequence tagged (EST) databases from both the public and private sector. Assigning gene function to these ESTs is now one of the major challenges in wheat genomics. Hypothesis testing strategies based on high-resolution EST mapping, candidate gene analysis, gene expression profiling, and proteomics are being used as entry points towards assigning gene function. Improving transformation efficiency as well as selection strategies for high throughput mutagenesis experiments will be two critical areas of research for the ultimate assignment of function to the numerous wheat genes that are being discovered using the new genomic tools. © 2001 Éditions scientifiques et médicales Elsevier SAS.