This chapter reviews the evolving definition of return on investment and value as it relates to healthcare information technology and explains the journey from Meaningful Use to High-Value Healthcare. It describes the incremental performance improvement to transformation and innovative disruption, the growing scope of healthcare change and expansion of key value themes. Value, or impact on enterprise performance, must be demonstrated and managed into reality. With value as the goal, healthcare information technology ability to enable performance improvement through improved business and clinical outcomes, reduced cost, and enhanced patient experience was examined in both quantitative and qualitative terms. The transition to high-value healthcare will accelerate the requirement to connect organizations, people, processes, data, and devices in new and different ways. Value and the ultimate return on investment will occur as the healthcare industry is transformed from volume to value, through clinically integrated, consumer centric, connected health and care.