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Based on the state of the art of health information systems (HIS) and the recent advancement in information and communication technology (ICT), we discuss the possible future HIS and their potential to transform the global health services. We also show why with all of the enabling technologies rapidly changing so many aspects of our daily life and environment, the actual impact of HIS on healthcare is much more limited than we think. We discuss the main reasons from the software engineering perspective and identify the challenges in the design and implementation of HIS to realize their perceived potentials. In the discussion of the causes of the challenges, we propose to apply model-driven software engineering methodologies to the design and analysis of future HIS, with the support of formal modeling and verification techniques and tools.