With the global international system in flux, changing from one dominated by the US to a more multipolar system, there is more opportunity for other major actors to impact international interactions. By integrating realist and constructivist approaches to transformations in the international system this paper will analyze the changing structure and patterns of interactions in the regional international system of the Middle East (ME) and their impact on the policy choices the actors are making. Major actors in the system include states such as the U.S., Turkey, Russia, Iran, and Saudi Arabia; quasi-states such as the Kurdish Regional Government; and non-state actors such as the Kurdish groups in Syria, Turkey and Iran as well as al Qaeda and its affiliates. Going back to its founding Turkey has looked to the West as a model of modernization and for security in the international arena especially through NATO. Turkey's alignment with the West and NATO has withstood periods of disagreements such as over Turkey's 1974 invasion of Cyprus and over Iran sanctions. Today there is an ideological shift in the AKP controlled Turkish government away from the West and a clash between Ankara and Washington over their national interests in the ME. Speculation abounds as to whether the U.S. and Turkey can continue to work together when Washington criticizes Ankara's human rights policies and foreign policy choices in strategic hot spots such as Syria and the Persian Gulf, over Russian arms acquisitions, and energy policy in the Mediterranean. The transformations in the global and regional international systems have given Russia renewed opportunity to play more aggressive roles in Eastern Europe as well as in the ME. Europe is also developing more independent policies, as are Saudi Arabia and Iran in the ME. China too is becoming more active on the world stage, though presently its strongest power plays are in the South China Sea. Outside of Asia, China sometimes seeks negotiating roles but most often its search for resources, investments and trade drives its foreign policies. The paper concludes that the transformations in the global and regional ME system have contributed to the increasingly tumultuous nature of the Turkish - U.S. relationship. Washington and Ankara should work harder to develop policies to reduce the tensions resulting from their competing national interests and their handling of identity issues in the ME.