The Cold War saw America completely abandon isolationism. The United States had been isolationist in the decade preceding World War II (1939–1945). During the decades following WWII, however, the United States became very active throughout most areas of the the world. Washington forged military alliances against communism. Communism was the philosophy of the Soviet Union—America's Cold War adversary. Washington sent economic aid to win friends and buttress friendly regimes. It also established permanent military bases in many countries. These steps were unprecedented, because isolationism had always been a key tenet throughout much of American history.

Europe was the most important battlefield of the Cold War. The United States built up West Germany as a bulwark against communism. Economic aid was dispatched to most European countries through the Marshall Plan (1948–1951). In 1949, The North Atlantic Treaty Organization—which linked the United States, Canada, and Western European nations—was founded. It was the most important military alliance of the Cold War.

In Asia, Washington was concerned by the rise of Communist China and preoccupied with wars in Korea and Vietnam. American troops fought in Korea (1950–1953) and Vietnam (1965–1973) in an effort to stop the spread of communism in those nations.

In Latin America, the United States intervened in some nations. Washington overthrew the president of Guatemala in 1954 and attempted to do the same in Cuba a few years later. President Ronald Reagan supported dictatorial governments in Central America during his administration. The US had meddled in Latin America long before the Cold War, but American involvement in the region deepened during the Cold War.

Washington and Moscow supported opposing sides in the Middle East. The US backed Israel, and the Soviets supplied the Arabs. The Israelis and the Arabs fought several wars. America also made alliances with Saudi Arabia and Iran; Washington's amicable relationship with Iran ended suddenly in 1979, though.

Although the Cold War ended decades ago, the United States remains heavily involved in all of these regions.