In recent years, the limiting factors for Genome-wide Association Studies (GWAS) in barley have shifted from the number of markers to the number of individuals, and to the deepness of phenotyping, particularly in field experiments of required size. Recent advances in methodology provide an increasing number of models available for research. This chapter provides an up-to-date review of issues relevant to GWAS approaches, with a particular focus on barley. The chapter offers an overview of all GWAS studies performed on barley and a summary of the results achieved. The chapter describes such methodological challenges as linkage disequilibrium, ascertainment bias, genetic and physical distances, resolution to single genes and the impact of population structure on detecting major loci in wheat. Finally, the chapter briefly introduces several new developments that enrich the outcome of GWAS studies, like genotype-environmental association suitable for landrace and wild materials, the inclusion of environmental effects to explain QTL effects, and the analysis of gene regulatory networks.