The Greek economy is being called upon to manage one of the highest proportions of public debt versus GDP in the European Union and the Euro zone. In turn, the healthcare sector is subject to the distortions of the Greek public sector, as there is no official method of measuring and evaluating the services being provided. OBJECTIVES: The objective of this analysis was both to interpret the development of pharmaceutical expenditure, based on the most significant changes in the pricing and reimbursement system, as well as to evaluate the institutional changes based on their effectiveness. METHODS: The analysis reflects the evolution of pharmaceutical expenditure and interprets the changes in the regulatory framework that took place in Greece from 1998-2008. It should be noted that there is significant confusion around the actual level of pharmaceutical expenditure, as the data provided for 2003 -2007 (provisional data) from the National Statistical Service of Greece are not in agreement with OECD’s data. Following a more careful analysis of the data, numerous questions arise with respect to their reliability, as there is no explanation for the apparent rate of change with regard to the factors that could influence expenditure (e.g. changes in the pricing or reimbursement system). Therefore the actual level of pharmaceutical expenditure is also in question. RESULTS: After analyzing the price changes in the top 100 selling pharmaceutical products in Greece, throughout the indicated period, it became obvious that the cause of increasing pharmaceutical expenditure cannot be attributed to increasing prices, but to other factors mainly associated with over-consumption. CONCLUSIONS: Finally, taking into account the intense pressures on public financing of the healthcare system, it is important for any future measures to constrain costs to be based on reliable and accurate data and to target the entirety of the system.