Concerns about the quality, safety, and cost of healthcare have driven the nation to increase its focus on this issue. A number of states are moving forward-in parallel with federal efforts-to develop and adopt policies for improving health and healthcare through health information technology and electronic health information exchange. Based on the eHealth Initiative's experience providing technical assistance to more than 20 states, and its work related to its coalition of more than 250 state, regional and community-based health information exchange initiatives and organizations, the most difficult challenges facing these initiatives and organizations today is that related to assessing the value of services that emerge from the health information exchange to various stakeholders groups such as providers, payers, and employers, and converting those value assessments to business plans that promote and assure sustainability for these initiatives. The combination of increased federal and state focus and funding and the pace at which regional and community-based health information networks are developing, along with the identification of value and sustainability as some of the most difficult challenges experienced by these efforts, all point to the significant need for evaluation. The most critical evaluation questions focus on the impact of health information technology and health information exchange on quality, safety, efficiency, the value of such efforts for various stakeholders, and assessment of how grant programs can be designed to support positive impact, value, and a sustainable business model, so that efforts continue when the grant funds are fully expended.