Many of the most dramatic and surprising effects of global change on ecological systems will occur across large spatial extents, from regions to continents. Multiple ecosystem types will be impacted across a range of interacting spatial and temporal scales. The ability of ecologists to understand and predict these dynamics depends, in large part, on existing site-based research infrastructures that were developed in response to historic events. Here we review how unevenly prepared ecologists are, and more generally, ecology is as a discipline, to address continental-scale questions given these pre-existing site-based capacities, and we describe the changes that will be needed to effectively pursue these broad-scale questions in the future. We first review the types of approaches commonly used to address questions at broad scales, and identify the research, cyber-infrastructure, and cultural challenges associated with these approaches. These challenges include developing a detailed, mechanistic understanding of the drivers and responses of ecosystem dynamics across a large, diverse geographic extent. Measurements of fluxes or flows of materials, energy or information across levels of biological organization or spatial units are challenging for the mosaic of natural and human-dominated ecosystems found across large spatial extents. The diversity of methods, sampling protocols, and data acquisition technologies make post-hoc comparisons of ecosystems using existing data challenging, and data collected using standardized methods across sites require coordination and teamwork. Sharing of data and analytics to create derived data products are needed for multi-site studies, but this level of collaboration is not part of the current ecological culture. We then discuss the strengths and limitations of current site-based research infrastructures in meeting these challenges, and describe a path forward for continental-scale ecological research that integrates existing infrastructures with emerging technologies to more effectively address broad-scale questions.