Foxtail millet (Setaria italica) is a major C4 minor cereal crop in northern China, characterized by strong adaptability such as drought and poor-soil tolerance. Its wild relatives harbor abundant genetic diversity and constitute an important gene pool for broadening the genetic base of cultivated foxtail millet and for breeding new cultivars with improved stress tolerance, high yield, and superior quality. This review focuses on the domestication and utilization of foxtail millet and its wild relatives. By integrating archaeological and genetic evidence, we summarize the origin and domestication trajectory of foxtail millet in northern China and highlight the evolution of key domestication-related traits. From a taxonomic perspective, we synthesize recent progress in both traditional morphology and molecular phylogenetics, and summarize the classification of genome types within the genus Setaria and its value for resolving phylogenetic relationships among related taxa. We further compile the current status of germplasm conservation and the current status of germplasm conservation and utilization of foxtail millet and its wild relatives, noting that China has an advantage in the overall number of conserved foxtail millet accessions, whereas the international coverage of the resources, as well as the representativeness and depth of characterization for wild relatives still need to be strengthened. Finally, we discuss their potential applications in germplasm innovation and breeding, in light of advances in genetic linkage maps/QTL mapping and GWAS, studies on stress tolerance and quality traits, and developments in transformation systems, genome editing, and molecular breeding. This review provides a reference for the systematic mining and efficient utilization of wild relative resources in foxtail millet.