The success of new innovations and technologies are very often disruptive in nature. At the same time, they enable novel next generation infrastructures and solutions. These solutions introduce great efficiencies in the form of efficient processes and the ability to create, organize, share and manage knowledge effectively; and the same time provide crucial enablers for proposing and realizing new visions. In this paper, we propose a new vision of the next generation healthcare enterprise and discuss how Translational Medicine, which aims to improve communication between the basic and clinical sciences, is a key requirement for achieving this vision. This will lead therapeutic insights may be derived from new scientific ideas - and vice versa. Translation research goes from bench to bedside, where theories emerging from preclinical experimentation are tested on disease-affected human subjects, and from bedside to bench, where information obtained from preliminary human experimentation can be used to refine our understanding of the biological principles underpinning the heterogeneity of human disease and polymorphism(s). Informatics and semantic technologies in particular, has a big role to play in making this a reality. We identify critical requirements, viz., data integration, clinical decision support and knowledge maintenance and provenance; and illustrate semantics-based solutions wrt example scenarios and use cases.