Cost-of-illness (COI) was the first economic evaluation technique used in the health field. The principal aim was to measure the economic burden of illness to society. Its usefulness as a decision-making tool has however been questioned since its inception. The main criticism came from welfare economists who rejected COIs because they were not grounded in welfare economics theory. Other attacks related to the use of the human capital approach (HCA) to evaluate morbidity and mortality costs since it was said that the HCA had nothing to do with the value people attach to their lives. Finally, objections were made that COI could not be of any help to decision makers and that other forms of economic evaluation (e.g. cost-effectiveness, cost-benefit analysis) would be much more useful to those taking decisions and ranking priorities. Conversely, it is here suggested that COI can be a good economic tool to inform decision makers if it is considered from another perspective. COI is a descriptive study that can provide information to support the political process as well as the management functions at different levels of the healthcare organisations. To do that, the design of the study must be innovative, capable of measuring the true cost to society; to estimate the main cost components and their incidence over total costs; to envisage the different subjects who bear the costs; to identify the actual clinical management of illness; and to explain cost variability. In order to reach these goals, COI need to be designed as observational bottom-up studies.