In this historical analysis of US foreign policy toward Iran during the presidency of George W. Bush, the author aims to decipher the overarching policy approach guiding United States' Iran policy in the context of the main issues arising during this time period. George W. Bush started his presidency with the legacy of past presidents, viewing Iran as a threat to US interests and drawing from the policy tool box that had been developed during the previous four administrations. In this paper, the implementation of these different policy approaches will be discussed in the context of the events of September 11, the Afghanistan and the Iraq wars, and the nuclear issue. Engagement, containment, and covert and overt means of destabilizing the Islamic Republic of Iran will be discussed. The roots of many of the current issues in U.S. -Iran relations as well as the tactics used to tackle them could be traced to the period under study. In the years after the presidency of George W. Bush and despite the different tactics used, this mentality has led presidents as diverse as Obama and Trump to suffer from the same strategic mistake: an instrumental approach to Iran. The failure of the Joint Comprehensive Plan of Action to withstand the transfer of power in the United States shows how the American practice of the weaponization of all available means to deal with Iran, including diplomacy and economic tools, is jeopardizing any real hope for a different direction in US-Iran relations.