Over the past four decades, American universities and colleges have internationalized so significantly that many are now global knowledge institutions. After a brief survey and categorization of different approaches to internationalization (from enhanced study abroad partnerships to full degree-granting campuses of U.S.-based institutions abroad), the essay presents a case study of NYU Abu Dhabi, which the author helped create as its first provost and later led as its vice chancellor. The analysis focuses on the rationale, challenges, and rewards for U.S. universities to engage seriously abroad, and argues that in the face of deglobalizing headwinds, universities need to strengthen, not attenuate, their efforts to promote research across borders and offer vigorous intercultural education.