A number of states, regions and communities across the U.S. are mobilizing healthcare information across organizations to improve health and healthcare through multi-stakeholder collaborative efforts. These initiatives involve a broad range of participants, including hospitals and other healthcare providers, physician practices, health plans, employers and other healthcare purchasers, laboratories, pharmacies, public health agencies, state and local governmental agencies, and most importantly, patients. In May 2005, the eHealth Initiative Foundation (eHI) launched its Second Annual Survey of State, Regional and Community-based Health Information Exchange Initiatives and Organizations. Responses from 109 health information exchange (HIE) efforts are included in our analysis of survey results. The survey includes questions about goals, objectives and functionality; organizational and governance models; financing and sustainability; policies for information-sharing; legal issues; and technical strategies. Self-reported information from the 109 initiatives across 45 states and the District of Columbia is a significant representation of the collective voice of the health information exchange community. This report documents the emerging trends, issues and challenges facing this community across the U.S.