In the past several years, huge investments have been made in enterprise resource planning (ERP) systems and related applications. While the integrated database and data warehouse in such systems provides value, more value could be realized if the databases could more semantically reflect the underlying reality of the organization. Inter-enterprise commerce can be facilitated with the use of ontologically based systems with common semantics (Geerts and McCarthy, 2000; Haugen and McCarthy, 2000) instead of reliance on electronic data interchange (EDI) standards. This chapter presents a normative semantic model for enterprise information systems that has its roots in transaction processing information systems. Empirical research on semantically modeled information systems is reviewed and an example company’s semantic model is provided as a proof of concept. This model is used as the basis for a discussion of its application to ERP systems and to inter-organizational systems. Future trends and research directions are also discussed.