This chapter explores the political significance of each form of unilateralism in the context of efforts by successive US administrations to limit drug trafficking and to regulate illegal immigration from Mexico into the United States. The drug war indeed turn out to be an opportunity to bring the United States and Mexico closer, but it remains foremost an extraordinarily dangerous and destructive challenge that may have been avoidable had different policies been pursued. In addition to its human and institutional costs. The drug was has for the time being sidelined any further cooperative work on the historically most important bilateral political issue immigration reform. Drug interdiction efforts starting with the Nixon administration, the early efforts by the George W. Bush administration to cooperate with Mexico on immigration reform, the breakdown of US Mexico cooperative efforts due largely to American unilateralism in both Mexico and, surprisingly, Iraq, and finally the recent emergence of the Mexican drug war.