Effective and appropriate implementation of health information systems assists with an organization’s knowledge management. To enhance a user’s trustworthiness and full adoption, a health information system needs to be dependable. This chapter reviews the different development methodologies available for engineering dependable solutions and their application by citing two case studies as an example. Health information systems cover a diverse set of applications. The focus in this chapter is on the development of electronic health record systems, the importance of dependability, and the relationship between dependability and data quality of the health record systems.