The genus Sechium P. Browne (Cucurbitaceae) comprises five taxa, all native to Mexico and Central America. It includes four wild taxa (Sechium chinantlense, Sechium compositum, Sechium hintonii, Sechium edule ssp. sylvestre) and one cultivated subspecies (Sechium edule ssp. edule), commonly known as “chayote.” Chayote is a perennial climbing plant with unisexual flowers, cross-pollination, and viviparous seeds. Its cultivation, which dates back at least 500 years, has focused primarily on fruit production, while recent studies have highlighted its antioxidant and lipid-lowering properties. The domestication process of S. edule remains unclear, due to the perishable nature of its seeds and the lack of archaeological evidence. Mexico is considered the center of genetic diversity for S. edule, although environmental pressures such as food demand, climate change, and deforestation threaten both the cultivated varieties and wild species. This chapter examines our current knowledge of the genus. We review the still unclear phylogenetic relationships within the genus using molecular markers and discuss other morphological, genetic, conservation and domestication aspects. Oaxaca and Veracruz are proposed as potential domestication centers of chayote, based on the presence of wild species, significant morphological and genetic similarities, and ethnolinguistic evidence. We provide insights for the conservation and genetic improvement of chayote based on evolutionary knowledge and agricultural needs.