This third and final installment of this series on innovative designs for the smart ICU addresses the steps involved in conceptualizing, actualizing, using, and maintaining the advanced ICU informatics infrastructure and systems. The smart ICU comprehensively and electronically integrates the patient in the ICU with all aspects of care, displays data in a variety of formats, converts data to actionable information, uses data proactively to enhance patient safety, and monitors the ICU environment to facilitate patient care and ICU management. The keys to success in this complex informatics design process include an understanding of advanced informatics concepts, sophisticated planning, installation of a robust infrastructure capable of both connectivity and interoperability, and implementation of middleware solutions that provide value. Although new technologies commonly appear compelling, they are also complicated and challenging to incorporate within existing or evolving hospital informatics systems. Therefore, careful analysis, deliberate testing, and a phased approach to the implementation of innovative technologies are necessary to achieve the multilevel solutions of the smart ICU.