This article historicizes the emergence of border studies in the south of Mexico, and offers an interdisciplinary perspective on the formation of the Mexico-Guatemala border. From a historical and anthropological perspective, we illustrate Fábregass (1994) thesis that All México is a frontier, with examples of the regional dynamics generated by narco trafficking, the migration of undocumented workers, the circulation of tourists and indigenous traders, and the political ecology of conservation agencies in border areas, all of which demonstrate transnational connections between northern and southern Mexico. The text offers a holistic view of both sides of the border with a review of important bibliographic sources.