Assessment of the human health risk posed by global climate change presents a new challenge to public health professionals. In contrast to conventional toxicological risk assessment, the health risk assessment related to global climate change must analyze stressors that consist of complex interrelated climate factors and risks that are mediated through intermediate species in varying ecosystems. A framework for ecologically based human health risk assessment helps distinguish the concepts of global climate change risk assessment from conventional risk assessment. Specific methods for linking climate variables with human disease include historical analysis of climate and disease data and the development of integrated mathematical models. Two historical climate-disease studies of malaria in Africa provide a starting point for further analysis. Early approaches to evaluating the human health risks from global climate change will include simple mapping of disease boundaries and climate factors. Computer-based geographical information system (GIS) technology will assist in the organization and analysis of climate, environment and disease data. Ultimately, complex integrated mathematical models may provide quantitative estimates of risk, but these models have not yet been validated. The collection of geographically organized relevant data through either field work or remote sensing technology will both help validate comprehensive integrated models and enhance our understanding of the associations between climate change and human health.