Biodiversity collections are experiencing a renaissance fueled by the intersection of informatics, emerging technologies, and the extended use and interpretation of specimens and archived databases. This paper explores the potential for transformative research in ecology integrating biodiversity collections, stable isotope analysis (SIA), and environmental informatics. Like genomic DNA, SIA provides a common ‘currency’ interpreted in the context of biogeochemical principles. Integration of SIA data across collections allows for evaluation of long-term ecological change at continent-wide scales. Challenges, including analysis of sparse samples, lack of isotopic baselines, and effects of preservation remain but none are insurmountable. The general research framework proposed here interfaces with databases and observatories, such as the National Ecological Observatory Network (NEON), to provide baselines for retrospective studies and ecological forecasting. Collections and SIA add historical context to fundamental questions in freshwater ecological research, baselines for ecosystem monitoring, and a means of quantitative assessment for ecosystem restoration.