This paper reviews and discusses the main procedures and policies that need to be followed when designing and implementing a binational survey such as the United States of America (U.S.)-Mexico Border Diabetes Prevalence Study that took place between 2001 and 2002. The main objective of the survey was to determine the prevalence of diabetes in the population 18 years of age or older along U.S.-Mexico border counties and municipalities. Several political, administrative, financial, legal, and cultural issues were identified as critical factors that need to be considered when developing and implementing similar binational projects. The lack of understanding of public health practices, implementation of existing policies, legislation, and management procedures in Mexico and the United States may delay or cancel binational research, affecting the working relation of both countries. Many challenges were identified: multiagency/multifunding, ethical/budget clearances, project management, administrative procedures, laboratory procedures, cultural issues, and project communications. Binational projects are complex; they require coordination between agencies and institutions at federal, state, and local levels and between countries and need a political, administrative, bureaucratic, cultural, and language balance. Binational agencies and staff should coordinate these projects for successful implementation.