Estimating the economic value to societies of health research is a complex but essential step in establishing and justifying appropriate levels of investment in research. The practical difficulties encountered include: identifying and valuing the relevant research inputs (when many pieces of research may contribute to a clinical advance); accurately ascribing the impact of the research; and appropriately valuing the attributed economic impact. In this review, relevant studies identified from the literature were grouped into four categories on the basis of the methods used to value the benefits of research. The first category consists of studies that value the direct cost savings that could arise from research leading either to new, less-costly treatments or to developments such as vaccines that reduce the number of patients needing treatment. The second category comprises studies that consider the value to the economy of a healthy workforce. According to this "human capital" approach, indirect cost savings arise when better health leads to the avoidance of lost production. The third category includes studies that examine gains to the economy in terms of product development, consequent employment and sales. The studies placed in the fourth category measure the intrinsic value to society of the health gain, by placing a monetary value on a life. The review did not identify any consistency of methodology, but the fourth approach has most promise as a measure of social value. Many of the studies reviewed come from industrialized nations and a proposal is made by the present reviewers for an international initiative, covering developed and developing countries, to undertake further methodological analysis and testing.