The 21st century started with some significant efforts globally in the e-health sector. This was mainly pushed as a generic strategy from many nations and international organizations in order to cope with issues such as ageing population, demographic shift, social security limitations, and financial instability. A second reason was the introduction of new technologies such as cloud computing, Web interoperability standards, mobile health, and social media that are steadily changing the way healthcare has been seen in the last decades. In addition to that, globalization, commuting, immigration, and increased mobility raised the issue of cross-border healthcare and the right to access normalized healthcare services anywhere, anytime. In that context, the authors analyze the technological offerings and result of the epSOS (European Patient Smart Open Services) framework and how it has affected strategic decisions in electronic prescription in Greece, thus creating a new useful e-health national application. They prove that by rethinking healthcare, reusing established standards such as HL7 CDA (Health Level Seven Clinical Document Architecture) and IHE (Integrating the Healthcare Enterprise) profiles, it is possible to propose a new innovative system that is in fact based upon new technological propositions such as REST (Representational State Transfer) architecture and cloud computing.