Health information systems (HIS) in their current form arerarely sustainable. In order to sustain our health information systems and with it our health systems, we need to focus on defining and maintaining sustainable Health Information System building blocks or components. These components need to be easily updatable when clinical knowledge (or anything else) changes, easily adaptable when business requirements or processes change, and easily exchangeable when technology advances. One major prerequisite for this is that we need to be able to define and measure sustainability, so that it can become one of the major business drivers in HIS development. Therefore, this paper analyses general definitions and indicators for sustainability, and analyses their applicability to HIS. We find that general ‘Emergy analysis’ is one possibility to measure sustainability for HIS. Based on this, we investigate major enablers and inhibitors to sustainability in a high level framework consisting of four pillars: clinical, technical, socio-technical, and political/business.