The hydrology and aquatic ecology of arid environments has long been understudied relative to temperate regions. Yet spatially and temporally intermittent and ephemeral waters characterized by flashy hydrographs typify arid regions that comprise a substantial proportion of the Earth. Additionally, drought, intense storms, and human modification of landscapes increasingly affect many temperate regions, resulting in hydrologic regimes more similar to aridlands. Here we review the contributions of Dr. Nancy Grimm to aridland hydrology and ecology, and applications of these insights to urban ecosystems and resilience of social-ecological-technological systems. Grimm catalyzed study of nitrogen cycling in streams and characterized feedbacks between surface water-groundwater exchange, nitrogen transformations, and aquatic biota. In aridlands, outcomes of these interactions depend on short- and long-term variation in the hydrologic regime. Grimm and colleagues applied hydrological and biogeochemical insights gained from study of aridland streams to urban ecosystems, integrating engineering, social and behavioral sciences, and geography. These studies evolved from characterizing the spatial heterogeneity of urban systems (i.e., watersheds, novel aquatic systems) and its influence on nutrient dynamics to an approach that evaluated human decision-making as a driver of disturbance regimes and changes in ecosystem function. Finally, Grimm and colleagues have applied principles of urban ecology to look toward the future of cities, considering scenarios of sustainable and resilient futures. We identify cross-cutting themes and approaches that have motivated discoveries across Grimm’s multi-decadal career, including spatial and temporal heterogeneity, hydrologic connectivity and regime, disturbance, systems thinking, and resilience. Finally, we emphasize Grimm’s broad contributions to science via support of long-term research, dedication to mentoring, and extensive collaborations that facilitated transdisciplinary research.