Diabetes is a serious public health problem in the border region between the United States of America and Mexico, reflecting and by some measures surpassing the extent of national diabetes burden of each country. The U.S.-Mexico Border Diabetes Prevention and Control Project, a two-phase prevalence study on type 2 diabetes and its risk factors, was conceived and developed by culturally diverse groups of people representing more than 100 government agencies and nongovernmental organizations; health care providers; and residents of 10 U.S. and Mexican border states, using a participatory approach, to address this disproportionate incidence of diabetes. This report describes the project's history, conceptualization, participatory approach, implementation, accomplishments, and challenges, and recommends a series of steps for carrying out other binational participatory projects based on lessons learned.