In light of current pressures to limit health care expenditures, economic evaluations will continue to be conducted to help assess the value of new therapies or treatment programs. Although guidelines for the conduct of economic evaluations have been proposed, it is unlikely that a standard/common methodology will (or should) be used. Consequently, it is important that the reader/reviewer of such analyses be aware of the potential challenges or difficulties when evaluating these assessments. While not providing a comprehensive list of these challenges, it is hoped that this article will serve to bring awareness to some of these challenges in the design, analysis and interpretation of these evaluations.