Backgorund: Discoveries that emerging and re-emerging pathogens have their origin in environmental change has created an urgent need to understand how these environmental changes impact disease burden. In this article we present a framework that provides a context from which to examine the relationship between environmental changes and disease transmission and a structure from which to unite disparate pieces of information from a variety of disciplines. Methods: The framework integrates three interrelated characteristics of environment - disease relationships: a) Environmental change manifests in a complex web of ecologic and social factors that may ultimately impact disease; these factors are represented as those more distally related and those more proximally related to disease. b) Transmission dynamics of infectious pathogens mediate the effects that environmental changes have on disease. c) Disease burden is the outcome of the interplay between environmental change and the transmission cycle of a pathogen. Results: To put this framework into operation, we present a matrix formulation as a means to define important elements of this system and to summarize what is known and unknown about the these elements and their relationships. The framework explicitly expresses the problem at a systems level that goes beyond the traditional risk factor analysis used in public health, and the matrix provides a means to explicitly express the coupling of different system components. Conclusion: This coupling of environmental and disease transmission processes provides a much-needed construct for furthering our understanding of both specific and general relationships between environmental change and infectious disease.