Regional organizations (ROs) have come under pressure for reform because important stakeholders perceive them as illegitimate. The United Kingdom’s decision to leave the European Union or Donald Trump’s renegotiation of NAFTA are but two prominent examples. ROs react to these legitimacy challenges in ways extant theories of regionalism cannot fully explain because they fail to consider legitimacy and legitimation as important determinants of institutional design and behavior. To advance this research agenda, this note makes three contributions. First, it reviews major theoretical perspectives on regionalism to show how their neglect of legitimacy and legitimation results in a number of empirical puzzles. While theories of regionalism make tacit assumptions on the role of legitimacy for design and behavior of ROs, they rarely theorize these causal links explicitly and thus fail to explain legitimacy-driven phenomena. Second, it argues that growing global governance research on legitimacy and legitimation can help to address these puzzles. Third, the note concludes by suggesting a research agenda intended to explain the core puzzles of regional organization associated with the role of legitimacy and legitimation.