Multilateralism and the multilateral institutions face serious threats. This in turn threatens the continuing progress in solving critical global economic and social challenges: slowing global economic growth and recurring global financial crises; growing inequality and—despite significant improvements in living conditions worldwide in recent decades—persistent deprivation due to poverty, hunger, conflict and fragility, especially in Africa; rising challenges to an open global trading regime; and the pervasive risks of pandemics, natural disasters, and climate change. This article aims to assess the threats faced by multilateralism and multilateral institutions and to develop some ideas on how they might be addressed. Just to be clear, though, multilateralism is not just about the financing of investments. It is also very important about developing and maintaining rules-based and fair global economic and social relations among countries and peoples, about setting widely accepted norms and monitoring their adherence, about establishing networks to create, collect, and exchange knowledge and data, and about resolving potential conflicts among partners and competitors for global resources, markets, and influence.