The introduction of electronic health records (EHRs) to the clinical setting has led healthcare professionals, policy makers, and administrators to believe that health information systems will improve the functioning of the healthcare system. In general, such expectations of health information system functionality, impact, and ability to disseminate have not been met. In this chapter the authors present the findings of three empirical studies: (1) the structured monitoring of EHR implementation processes in Denmark from 1999–2006 by the Danish EHR observatory, (2) a usability study based on human factors engineering concepts with clinicians in artificial but realistic circumstances—a “state of the art (2005)” for Danish CPOE (computerized physician order entry system), and (3) user reactions to a conceptual “high level model” of healthcare activities—the Danish G-EPJ model in order to better understand the reasons for health information system failures and to suggest methods of improving adoption. The authors suggest that knowledge handling as a science seems immature and is not in line with the nature of clinical work. The prerequisites for mature knowledge handling are discussed in the second part of this chapter. More specifically, the authors describe one way of improving knowledge handling: the development of a more true digital representation of the object of interest (OOI) or the virtual patient/citizen that interacts with computer based healthcare services on behalf of and for the benefit of the citizen’s health.