The US government has proposed the development of scientific centers of excellence to solve global challenges. We propose such a center of excellence devoted to the genomic analysis of Mediterranean populations of all creeds. This genomic focus is rooted in the region’s demographic history, builds on the area’s rapidly developing expertise in human genetics, and will yield scientific discoveries of both local and global significance. The genome sequence data of Mediterranean populations will offer unique insights into human evolution and early human migration. The potent combination of highly consanguineous populations in the Mediterranean’s southern and eastern rims and regional medical and scientific expertise could lead to the identification and characterization of many genes responsible for human disease. Such discoveries will enable genetic knowledge to be translated into medical knowledge that will benefit local populations and contribute substantially to the understanding of the genetic bases of human diseases worldwide.