Emerging infectious diseases (EIDs) pose international security threats because of their potential to inflict harm upon humans, crops, livestock, health infrastructure, and economies. Despite the scale of this threat, there are inherent limitations in preventing and controlling EIDs, including the scope of current disease surveillance efforts. All of this leads to the following questions in the context of Mexico’s recent swine flu experience: What were the cultural, political, and economic challenges to Influenza A/H1N1 virus response in Mexico? By way of comparison, what can we learn from the U.S. experience in 1976 with A/New Jersey/76 (Hsw1N1), later referred to as H1N1? This article explores the comparative political economy of Mexico’s handling of influenza virus A/H1N1 outbreak in 2009. Research provides notable observations-based on the strengths and weaknesses of each country’s response–that can be used as a starting point of discussion for the design of effective EIDs surveillance programs in developing and middle-income countries. In the U.S., the speed and efficiency of the 1976 U.S. mobilization against H1N1 was laudable. Although the U.S. response to the outbreak is seldom praised, the unity of the scientific and political communities demonstrated the national ability to respond to the situation. Mexico’s strongest characteristics were its transparency, as well as the cooperation the country exhibited with other nations, particularly the U.S. and Canada. While Mexico showed savvy in its effective management of public and media relations, as the article details, political, economic, and cultural problems persisted.