Large-scale economically-driven encroachments into tropical rainforest environments are major factors for disease emergence. A better understanding of the process of disease emergence can be best derived from a multilevel, transdisciplinary ecosystem approach that analyzes health data in its biological, ecological, social, and cultural context. Multiple methods, including ethnographic techniques, are recommended for such an approach. The value of this approach and methodology is presented in this article through a rapid health assessment case study of an unexplained fatal syndrome that occurred among the Secoya peoples of the Ecuadorian Amazon in 1999. This type of study is significant given the lack of health data for indigenous populations at risk of disease emergence. Moreover, indigenous cultures share a long-term, close relationship to the land and each other, which makes information about changes in their environment and health patterns highly salient to them. This local knowledge is of strategic value to researchers working on issues of environmental change and disease emergence.