This Special Issue is intended to highlight both recent work to advance the physical understanding of transboundary aquifers and factors relevant in successful collaboration on transboundary groundwater resource use. The collected papers address: (1) the identification and prioritization of the needs and strategies for sustainable groundwater development and use, along with the complexities introduced by working across borders with differing governance frameworks, institutions, cultures, and sometimes languages; (2) the characterization of the physical framework of the aquifer, stressors on the aquifer system, and how those stressors influence the availability of groundwater in terms of its quantity and quality; and (3) the incorporation of stakeholder input and prioritization directly into the process of aquifer assessment and model building. The papers provide insights into the state of knowledge regarding the physical characterization of important transboundary aquifers, primarily along the U.S.–Mexico border and the opportunities for greater stakeholder involvement in resource evaluation and prioritization. They point the way towards a future focus that combines both of these aspects of transboundary aquifer assessment for informing groundwater management discussions by policymakers.