Regional Health Information Organizations (RHIOs) in rural areas promise improved health care for many underserved populations. However, implementation in rural areas faces many challenges. One of the most rural states in the United States is in the process of creating a second comprehensive health information network and offers an opportunity to look at success factors for implementation of rural RHIOs. Methods: Documentation was reviewed and summarized and a core group of Vermont Information Technology Leaders (VITL, Inc.) were interviewed to ascertained lessons learned in the development of Vermont's RHIO. Results: Lessons were grouped into five major categories: early planning, organization, education and marketing, technology, and financial sustainability. Conclusion: There are a number of commonalities about all RHIOs but also a number of differences predicated on location. RHIOs must remain dynamic and learn from others in order to survive.