The relationship between the United States and the Islamic Republic of Iran both shapes and is shaped by a new Middle Eastern “Cold War”. The United States and the Islamic Republic should transcend the prospects for hegemonial conflict or strategic standoff and seek a fundamental realignment of their relations, along the lines of the realignment in relations between the United States and the People's Republic of China that took place during President Richard Nixon's tenure in the White House. The article examines the imperatives for a comprehensive and strategic realignment of US–Iranian relations from the standpoint of Iranian interests and foreign policy concepts as well as from an American perspective. It also evaluates the actual prospects for US–Iranian rapprochement.