In this study we examined the origins and consequences of HIV/AIDS-related stigma on the Mexican-Guatemalan border. To explore these issues, an inductive/deductive approach was taken. Data were collected using qualitative methods including nonparticipant observation, in-depth interviews, and informal conversation. Informants included Central American immigrants, locals, and contextual key informants. Findings reveal that gender, social class, and race/ ethnicity function as key determinants of HIV/AIDS-related stigma, but serve also as the basis around which migration-related stigma is constructed within this particular context. These issues need to be taken into account in addressing the vulnerability of mobile populations, as well as the stigma attached to migration and HIV/AIDS. To be effective, responses should be based in the social and contextual realities faced by migrants and mobile populations, and be part of a more general process of empowerment that improves their legal, social, economic, and health status.