Over the more than two decades of free trade between Mexico and the United States (1994-2018), there has been an important alignment between the countries on strategic and security matters. This paper provides a road map for U.S.-Mexico bilateral cooperation on security matters for the next six years, under the presidency in Mexico of Andrés Manuel López Obrador. It offers concrete and implementable policy recommendations for the current context of U.S.-Mexican relations. Our recommendations for advancing Mexican and U.S. interests and promoting effective cooperation broadly fall into three categories of joint policy action: (1) aligning policy objectives, (2) deepening subnational cooperation, and (3) addressing chronic irritants.