Specific HLA associations with drug hypersensitivity may vary between geographic regions and ethnic groups. There are little to no data related to HLA-drug hypersensitivity on populations who reside in the Greater Middle East (GME), a vast region spanning from Morocco in the west to Pakistan in the east. In this review, the authors intended to summarize the significant HLA alleles associated with hypersensitive drug reactions induced by different drugs, as have been found in different populations, and to summarize the prevalence of these alleles in the specific and diverse populations of the GME. For example, HLA-B*57:01 allele prevalence, associated with abacavir-induced hypersensitivity, ranges from 1% to 3%, and HLA-DPB1*03:01 prevalence, associated with aspirin-induced asthma, ranges from 10% to 14% in the GME population. Studying pharmacogenomic associations in the ethnic groups of the GME may allow the discovery of new associations, confirm ones found with a low evidence rate and enable cost-effectiveness analysis of allele screening before drug use.