The past few decades have witnessed hundreds of family-based linkage studies mapping for numerous traits but only a limited number of QTLs were actually cloned, tagged, or used for marker-assisted selection. Although providing valuable information, this conventional approach cannot be scaled up to underpin the incredible amount of phenotypic variation in the form of 266, 589 hexaploid wheat accessions maintained in public germplasm collections. Association mapping has recently emerged as an alternative and more powerful mapping approach where a natural population is surveyed to determine marker-trait associations using linkage disequilibrium (LD). After its first application for milling quality in 2006, association mapping studies in hexaploid wheat are being extended to tag yield traits, protein quality, and tolerance to biotic and abiotic stresses. Advances in genotyping technology and statistical approaches greatly accelerated the shift from conventional linkage-based mapping to LD-based association mapping. Association mapping stands out because of simultaneous utilization of a large number of ex situ-conserved natural variation due to historical recombination events accumulated over centuries.