The use of plant genetic resources (PGR)—wild relatives, landraces, and isolated breeding gene pools—has had substantial impacts on wheat breeding for resistance to biotic and abiotic stresses, while increasing nutritional value, end‐use quality, and grain yield. In the Global South, post‐Green Revolution genetic yield gains are generally achieved with minimal additional inputs. As a result, production has increased, and millions of hectares of natural ecosystems have been spared. Without PGR‐derived disease resistance, fungicide use would have easily doubled, massively increasing selection pressure for fungicide resistance. It is estimated that in wheat, a billion liters of fungicide application have been avoided just since 2000. This review presents examples of successful use of PGR including the relentless battle against wheat rust epidemics/pandemics, defending against diseases that jump species barriers like blast, biofortification giving nutrient‐dense varieties and the use of novel genetic variation for improving polygenic traits like climate resilience. Crop breeding genepools urgently need to be diversified to increase yields across a range of environments (>200 Mha globally), under less predictable weather and biotic stress pressure, while increasing input use efficiency. Given that the ~0.8 m PGR in wheat collections worldwide are relatively untapped and massive impacts of the tiny fraction studied, larger scale screenings and introgression promise solutions to emerging challenges, facilitated by advanced phenomic and genomic tools. The first translocations in wheat to modify rhizosphere microbiome interaction (reducing biological nitrification, reducing greenhouse gases, and increasing nitrogen use efficiency) is a landmark proof of concept. Phenomics and next‐generation sequencing have already elucidated exotic haplotypes associated with biotic and complex abiotic traits now mainstreamed in breeding. Big data from decades of global yield trials can elucidate the benefits of PGR across environments. This kind of impact cannot be achieved without widescale sharing of germplasm and other breeding technologies through networks and public–private partnerships in a pre‐competitive space.