Those in charge of directing scientific research face a daunting task: finding a proper balance between excellence in research and that research's relevance to people's health problems. In developing countries, this task is further hampered by deficient scientific and technological infrastructure, the lack of competitiveness of its research community, and the shortage of research funds. This article explains some of the mechanisms that have been put in place in Latin America to achieve a balance between excellence and relevance, especially by promoting research that targets pertinent public health problems. Within this context, the multicenter studies being conducted under the auspices of the Pan American Health Organization's Program for the Support of Research are described. The article also lays out the fundamental features of a new model for international cooperation to generate knowledge to help resolve the public health problems of the countries of the Americas.