BACKGROUND: MND results in progressive degeneration of the motor neurons, with intellect remaining largely unaffected. Average life expectancy from diagnosis to death is 2 – 5 years. Riluzole is the only treatment which has been shown to extend life in MND, though its cost-effectiveness has been questioned. In recent years, there has been a large increase in the number of EEs. Many have been criticised due to methodological deficiencies. Using MND as an example, it is clear that EEs can provide either valuable or misleading information in a decision-making context. METHODS: Systematic search for, and critical appraisal of, available EEs of riluzole therapy for MND. RESULTS: The methodological quality of the six identified studies was variable. The study with the greatest validity concluded that riluzole is a cost-effective intervention. Flaws in other studies related to the identification and measurement of costs, and to the extrapolation of benefits. Overall there was a range in the estimates of cost-effectiveness. For example, Messori et al (1999) calculated the incremental cost per life year gained to be approximately £41,000, whereas analysis by Tavakoli, et al. (1999) used Markov modeling to incorporate the importance of implications on quality of life in the remaining months. This methodology revealed that the incremental cost per life year gained was £8,587, and therefore identified riluzole as a cost-effective therapy. CONCLUSION: Clear presentation and use of perspective and relevant disease end-points are vital in economic evaluation to avoid paradoxes in results of studies assessing similar interventions. For therapies such as riluzole, where length of life and quality of life are key variables, different end-points can provide contradictory results.