The emergence of Arabidopsis as a model species and the availability of genetic and genomic resources have resulted in the identification and detailed characterization of abiotic stress signalling pathways. However, this has led only to limited success in engineering abiotic stress tolerance in crops. This is because there needs to be a deeper understanding of how to combine resistances to a range of stresses with growth and productivity. The natural variation and genomic resources of Arabidopsis thaliana (Arabidopsis) are a great asset to understand the mechanisms of multiple stress tolerances. One natural variant in Arabidopsis is the accession C24, and here we provide an overview of the increasing research interest in this accession. C24 is highlighted as a source of tolerance for multiple abiotic and biotic stresses, and a key accession to understand the basis of basal immunity to infection, high water use efficiency, and water productivity. Multiple biochemical, physiological, and phenological mechanisms have been attributed to these traits in C24, and none of them constrains productivity. Based on the uniqueness of C24, we postulate that the use of variation derived from natural selection in undomesticated species provides opportunities to better understand how complex environmental stress tolerances and resource use efficiency are co-ordinated.