Inappropriate polypharmacy issues have emerged in various settings and geographic areas in Greece, but efforts to articulate them and sensitize the public have been isolated rather than systematic so far. Although e-prescription implementation is widespread (≈98% coverage nationwide) and disease-specific guidelines (therapeutic protocols) have been developed, eprescription still remains in the “data recording” stage, polypharmacy management is only associated with direct economic indicators, and medication review policies, pharmacovigilance and reliable reporting (alert) systems are scarce or absent. Health spending has dropped since 2009, as a result of government-wide efforts focused on reducing the large budgetary deficit. Medication safety is not adequately taken into account and dispensing of OTC medicines through enterprises other than pharmacies may endanger prudent use of medicines (1). Electronic Patient Health Record and e-prescription data analysis have not been incorporated into the National Healthcare System infrastructure. Incentives and opportunities for participation in polypharmacy management and medication adherence programmes for health professionals or patients are fundamental. Collaboration of all stakeholders in healthcare, the establishment of the “case/care manager” and patient education remain unexploited drivers for change. Lack of coordination of institutions and authorities and overlap of their responsibilities, gaps in health care policies, healthcare workforce and infrastructure shortages, Primary Healthcare insufficiencies and cultural issues have become key barriers to the development of a strategic plan and the implementation and evaluation of relevant policies. Structured, comprehensive programmes and national, regional or local policies, guidelines and legislation regarding polypharmacy management and medication adherence have not yet been developed. In contrast, healthcare professionals design and participate in initiatives of medication management activities with the primary motive of improving their practice for their patients. However, these activities are local, restricted to health professionals and patients that wish to participate, are not reimbursed, are not supported by the state and are not scaled up. There is an urgent need to implement a polypharmacy management policy, by following both ‘topdown’ (from the State) and ‘bottom-up’ (from the society) approaches. This case study provides valuable insight into why there are not any policies regarding polypharmacy and adherence in Greece how relevant programmes could be developed, implemented and evaluated; and, explores which barriers and facilitators could have an impact on change.