Mexico is the center of origin and diversification of the genus Cucurbita, which includes 15 taxa. Of these, five are endemic to Mexico, and five are domesticated. In recent years, studies on domesticated taxa have increased significantly, especially from a genetic and evolutionary point of view. This chapter reviews recent advances in phylogenetic, genetic, and evolutionary analyses of all Mexican taxa, as well as population studies of domesticated taxa (C. argyrosperma ssp. argyrosperma, C. moschata, C. pepo subsp. pepo, and C. ficifolia) and their wild relatives. The genetic diversity of the Cucurbita species growing in Mexico and their relationship with climatic variables are analyzed in detail, including genomic aspects at the population level. The phylogeographic description of wild and domesticated taxa and analyses of their local adaptation are included to improve our understanding of the domestication and evolutionary processes within the genus. In addition, various genomic studies on different Cucurbita species and their comparative analyses in terms of molecular evolution are reviewed. Recent advances in comparative genomics are providing insights into the genomic changes associated with adaptation to different environmental conditions and key aspects of their domestication.