Economic and financial market risks; the consequences of climate change, terrorism, and organized crime; supply security of energy and raw materials; the increase of cybercrime; and the vulnerability of critical infrastructure—governments, businesses, and societies face numerous systemic risks. Purely national approaches to cope with these transnational challenges are doomed to fail. In fact, there is a need for international cooperation. The United States and the EU are key players in this context—without the two economic and political heavyweights, systemic risks cannot be handled adequately. Despite the high degree of integration of their economies, sound political relations, and similar vulnerabilities to systemic risks, cooperation between the two partners is often difficult.