Genome-wide association studies (GWASs) have been a crucial and powerful method for the elucidation of plant traits by studying natural genetic variation and linkage disequilibrium in different genotype populations. The chapter covers all the historical events, the basic theories, and all the methodological developments that have led to GWAS becoming a dominant tool in modern crop breeding. It discusses the main reasons for the success of GWAS, such as population structure, the choice of genotyping technology, statistical methods, and the increasing influence of multi-omics integration, machine learning, and high-throughput phenotypic evaluation on raising detection power and improving biological interpretation, all of which are already well acknowledged. This chapter also discusses the methods used to deal with population stratification, polyploid genomes, and the detection of rare alleles, which pose the main challenges. The authors present their vision of the future and the latest breakthroughs, where GWAS is still a fundamental instrument in the speedy production of climate-resilient and high-yielding varieties.