OBJECTIVES Orphan Drugs (ODs) are medicinal products intended for diagnosis, prevention or treatment of rare diseases. Access to ODs is crucial for patients' health and quality of life. The aim of this study was to identify current problems and future challenges of patients’ access to ODs in Greece. METHODS A qualitative study took place between December 2013 and January 2014. Data were retrieved through semi-structured interviews with six representatives of key stakeholders in Greece and policy documents identified through web searches using keywords "orphan drugs" and "rare diseases" in Greek. Web-based documents and transcribed interviews were content analyzed.  RESULTS Delays in pricing and reimbursement of ODs in the Greek pharmaceutical market, budget cuts in hospitals and absence of patient registries constitute according to the analysis the greatest barriers in patients' access to ODs. There are two main channels through which the patient can have access to an OD and it depends whether it is licensed in Greece or not. In the first case the patient can take the drug through the hospital or the pharmacy of EOPYY if it is not available at the hospital pharmacy and in the second case through a public sector organization (IFET). All cases are characterized by extensive bureaucracy and involvement of up to three organizations in order to receive the approval, a procedure creating delays in patients’ access and risking their health. Also, the absence of a well-described procedure and lack of cooperation between the organizations and committees create further delays. CONCLUSIONS Ensuring patients' access to ODs in Greece is challenging especially during the economic crisis. Financial constraints and continuous legislative changes in the health system and the pharmaceutical market constitute important barriers to patients' access. There is a need to describe, organize and communicate the pathway of patients' access to ODs.