Research to date has indicated that a range of environmental variables such as disease, parasitism, predation, competition, environmental contamination, solar ultraviolet radiation, climate change, or habitat alteration may be responsible for declining amphibian populations and the appearance of deformed organisms, yet in many cases no definitive environmental variable stands out as a causal factor. Multiple stressors are often present in the habitat, and interactions among these can magnify injury to biota. This raises the possibility that the additive or synergistic impact of these stressors may be the underlying cause of amphibian declines. Effective management for the restoration of amphibian populations requires the identification of causal factors contributing to their declines. A systematic approach to determine causality is especially important because initial impressions may be misleading or ambiguous. In addition, the evaluation of amphibian populations requires consideration of a broader spatial scale than commonly used in regulatory monitoring. We describe a systematic three-tiered approach to determine causality in amphibian declines and deformities. Tier 1 includes evaluation of historic databases and extant data and would involve a desktop synopsis of the status of various stressors as well as site visits. Tier 2 studies are iterative, hypothesis driven studies beginning with general tests and continuing with analyses of increasing complexity as certain stressors are identified for further investigation. Tier 3 applies information developed in Tier 2 as predictive indicators of habitats and species at risk over broad landscape scales and provides decision support for the adaptive management of amphibian recovery. This comprehensive, tiered program could provide a mechanistic approach to identifying and addressing specific stressors responsible for amphibian declines across various landscapes.