Regional international organizations have long been seen as important in the search for the most productive forms of global governance. Is this still the case in a world that today is often described as both globalized and fragmented? This chapter explores four forms of connectedness that challenge the continuing relevance of regions and regionalism to the future of governance—populism, transnationalism, new spatial forms, and geopolitics. While these features test the relevance of governance at the regional level, regional groupings will persist into the future. New forms of connectedness themselves often are generating regional level responses to significant transitions in domestic and global societies. This is not to deny that new forms of connectivity might strengthen at the expense of regionalism in ways that are unanticipated. Were this to happen, a more intense contest between organizational forms will ensue further complicating the international landscape and the future of global governance.