The increased accuracy of climate predictions, and improving understanding of interactions between weather and infectious disease, has motivated attempts to develop models to predict changes in the incidence of epidemic-prone infectious diseases. Such models are designed to provide early warning of impending epidemics which, if accurate, would be invaluable for epidemic preparedness and prevention. This document evaluates the potential of climate-based disease early warning as a means of improving preparedness for, and response to, epidemics. On the basis of the history of the development of early warning system (EWS) to date, the authors develop a conceptual framework for constructing and evaluating climate-based EWS. They identify the climate-sensitive diseases of major public health importance and review the current state of the art in climate-based modelling of these diseases, as well as future requirements and recommendations. It reviews the current state of development of EWS for a number of key infectious diseases. The last few years have seen rapid progress in research; many new studies have demonstrated significant associations between climate variability and infectious disease transmission, and have specifically highlighted the potential for developing climate-based EWS.