To help in understanding the manner in which community, individual, and other factors in the United States and Mexico contribute to drug use among transnational migrants, this paper introduces a binational social ecology model of substance abuse in this population. We draw on our two NIH-funded ethnographic studies—one on problem drinking, and the other on drug abuse—among transnational Mexican workers in the mushroom industry of southeastern Pennsylvania. Our model demonstrates that major reasons for substance abuse among transnational migrants include nontraditional living arrangements in labor camps and overcrowded apartments, the absence of kin and community deterrents to drug use, social isolation, the presence of drug use and binge drinking subcultures, the availability of drugs, family history of drugs, previous drug use or witnessing of drug use in Mexico, and drug use norms and drug availability in Mexico. It suggests the need for U.S. and Mexican researchers to collaborate in binational teams and address factors on both sides of the border. Our binational social ecology model, together with our research recommendations, will assist alcohol and drug researchers to discover how community and individual factors in both the United States and abroad fit and interact beyond mere association and provide a more comprehensive research approach to substance abuse research among transnational migrants.