The paper considers the evolution of Indian-American relations from the 1940s to the present. The regional dimension in Indian-American relations is characterized by extreme inconsistency. Thus, New Delhi, the historical leader of the Non-Aligned Movement, despite the change in world order due to the fall of the Iron Curtain, continues to abandon allied relations and, as a rule, pursues a balanced policy in all regions barring its own — South Asia. Being primarily a South Asian regional power, India uncompromisingly defends its national interests in conflicts with Pakistan and does not allow the Pakistan-US dialogue to intervene in the solution of the Kashmir problem. The United States, in turn, reneges its historic course of unequivocal support for Islamabad and multilateral dispute settlement mechanisms in favor of a balanced approach, namely favoring bilateral negotiations between the conflicting parties. An important element of changes in South Asia’s importance is the emergence of nuclear weapons in the region. The nuclear factor significantly complicates the already difficult relationship between New Delhi and Islamabad and reinforces concerns of the globe and Washington in particular. The terrorist threat emanating from Pakistan and neighboring Afghanistan adds instability to the already conflicting relations between the countries of the region. The withdrawal of the US troops from Afghanistan does not contribute to improving the security architecture as well. In general, South Asia, both historically and today, is not high on the American foreign policy agenda. Accordingly, India and Pakistan are more important for the United States in the broader context of the Indo-Pacific Strategy (India) and the Greater Middle East (Pakistan), or as separate actors in international relations that contribute to solving problems in a bilateral format rather than South Asian countries per se.