Induced mutations have been used to generate novel variation for breeding purposes since the early 1900s. However, the combination of this old technology with the new capabilities of high-throughput sequencing has resulted in powerful reverse genetic approaches in polyploid crops. Sequencing genomes or exomes of large mutant populations can generate extensive databases of mutations for most genes. These mutant collections, together with genome editing, are being used in polyploid species to combine mutations in all copies of a gene (homoeologs), and to expose phenotypic variation that was previously hidden by functional redundancy among homoeologs. This redundancy is more extensive in recently formed polyploids such as wheat, which can now benefit from the deployment of useful recessive mutations previously identified in its diploid relatives. Sequenced mutant populations and genome editing have changed the paradigm of what is possible in functional genetic analysis of wheat.