Calcium (Ca2+) signaling is integral to nearly all aspects of plant biology, including development and responses to biotic and abiotic stresses. It operates through two main layers: the generation of Ca2+ signals and their decoding by Ca2+-binding proteins, which act early in diverse signaling pathways. The system exhibits remarkable robustness and versatility, largely due to its network-like organization. While fundamental principles of Ca2+ signaling were initially established in noncrop model organisms, recent research has increasingly expanded toward major crop species and has demonstrated that natural and synthetically created variation in Ca2+ signaling components can shape agronomically important traits. In this review, we first provide a concise overview of the fundamental principles of plant Ca2+ signaling and then synthesize the current status of this research field in major crop plants. We discuss why exploiting existing natural and engineering synthetic genetic diversity in Ca2+ signaling components offers promising strategies to enhance crop stress resilience and yield stability. Subsequently, we delineate how – aided by artificial intelligence – superior alleles can be identified and/or created and incorporated into elite crop genomes. Finally, we discuss current challenges and emerging perspectives in translating Ca2+ signaling research into practical applications for crop improvement.
