The response is described to the 2010 call from the Pan American Health Organization to develop a Regional Framework on Core Competencies in Public Health, with a view to supporting the efforts of the countries in the Americas to build public health systems capacity as a strategy for optimal performance of the Essential Public Health Functions. The methodological process for the response was divided into four phases. In the first, a team of experts was convened who defined the methodology to be used during a workshop at the National Institute of Public Health of Mexico in 2010. The second phase involved formation of the working groups, using two criteria: experience and multidisciplinary membership, which resulted in a regional team with 225 members from 12 countries. This team prepared an initial proposal with 88 competencies. In the third phase, the competencies were cross-validated and their number reduced to 64. During the fourth phase, which included two workshops, in March 2011 (Medellín, Colombia) and June 2011 (Lima, Peru), discussions centered on analyzing the association between the results and the methodology.