The signing of the Joint Comprehensive Plan of Action (JCPOA) in July 2015 brought about an apparent resolution of the conflict over the Iranian nuclear programme and represented a major diplomatic achievement for all of the parties involved. It had, nevertheless, been a long time coming and arrived only after decades of ill-conceived American policies had failed to achieve their objectives.

Although formally beginning in 1957, the US–Iranian nuclear relationship only became a significant preoccupation for both states in the 1970s, following the dramatic escalation of the Shah's nuclear ambitions. His announcement of his grandiose new plan and the negotiations that followed quickly brought what would become perennial concerns to the fore. Although initially keen to help its ally, the Nixon administration soon became aware of the proliferation risks involved and the extent of congressional opposition to any agreement that would transfer reprocessing or other fuel cycle technology to Iran. For their part, the Shah and Akbar Etemad were adamant that Iran must have nuclear autonomy. It was incompatible with their nuclear ambitions, their understanding of the Treaty on the Non-Proliferation of Nuclear Weapons (NPT) and their national pride that Iran should be dependent on foreigners for the technology and material required to produce nuclear energy (and, if it became necessary, weapons). The irreconcilability of the two sides’ demands produced a deadlock that was only broken when the Shah, his grip on power already crumbling, conceded American demands in 1978. By then, however, it was too late, and the proposed new US–Iranian nuclear agreement was stillborn.

The Iranian Revolution and the birth of the Islamic Republic produced a fundamental transformation of the US–Iranian relationship. The conflict over Iran's right to the fuel cycle was dramatically exacerbated by the process of mutual demonisation which followed the Revolution. The American experience of the hostage crisis and Iran's experiences during the Iran–Iraq War forged a deep loathing and fear of the ‘other’ on both sides that would shape the nuclear relationship for the next three decades. What the majority of Americans took from the Revolution and the hostage crisis was the perception that Iran was now in the hands of a bunch of crazed religious fanatics who were bent on overthrowing America's allies and overturning the influence of the United States throughout the Middle East.