The Rio Grande Basin in New Mexico exemplifies the far-reaching and complex issues currently facing water management in the west.  In this study, investigation of Rio Grande salinity issues focused on identification of relative salinity contributions from anthropogenic and natural sources. A geochemical forensic approach was utilized to isolate specific contributors to observed salinization in the Rio Grande.  Success in our approach was assisted greatly by engaging multiple state agencies, technical firms, and analytical laboratories early in the design phase of the project.  Collaborative tasks included historical data review and quality assurance, sample collection, and final data interpretation.  This joint technical team relied on an existing conceptual model of the Rio Grande hydrologic environment to design the sampling schemes and select appropriate chemical and isotopic components to evaluate the hydrologic system.  In particular, the technical team selected isotopic candidates based on their applicability to this hydrologic system and the cost-effectiveness of the analysis.  Results using boron (δ¹¹B), sulfur (δ³⁴S), oxygen (δ¹⁸O), hydrogen (δD), strontium (⁸⁷Sr/⁸⁶Sr) as well as basic chemical data, confirmed the pre-project hypothesis of dominant salinity contributions from deep groundwater inflow to the Rio Grande.  The stable isotopic ratios identified the deep groundwater inflow as distinctive, and identified characteristic isotopic signatures.  The analytical results combined with simulated multi-component isotopic mixing and mass transfer modeling effectively eliminated evapotranspiration as the primary factor in observed Rio Grande salinization.  Although many forensic isotopic and chemical tools are potentially useful, utilizing the partnership of affected state agencies, technical firms, and laboratories allowed for development of a protocol that was efficient, focused, defensible, and cost-effective.