A study was conducted to examine the feasibility of estimating the global burden of disease due to fluoride in drinking water. Skeletal fluorosis is a serious and debilitating disease which, with the exception of one area in China, is overwhelmingly due to the presence of elevated fluoride levels in drinking water. The global burden of disease due to fluoride in drinking water was estimated by combining exposure-response curves for dental and skeletal fluorosis (derived from published data) with model-derived predicted drinking water fluoride concentrations and an estimate of the percentage population exposed. There are few data with which to validate the output but given the current uncertainties in the data used, both to form the exposure-response curves and those resulting from the prediction of fluoride concentrations, it is felt that the estimate is unlikely to be precise. However, the exercise has identified a number of data gaps and useful research avenues, especially in relation to determining exposure, which could contribute to future estimates of this problem.