Profiles in Science, a Web-accessible digital library showcasing the personal manuscript collections of several Nobel Prize winning scientists and other prominent biomedical researchers and leaders in public health, has been publicly available since September 1998 through the National Library of Medicine (NLM) at the National Institutes of Health, U.S. Department of Health and Human Services. Profiles in Science features digital reproductions of historical items selected from the archival collections of the NLM as well as from collaborating institutions. In addition to the expected challenges posed by technological evolution, our experience with Profiles in Science over the years has taught us that change affects virtually every area of our project, including established procedures, project mission, legal considerations, and stakeholder expectations. Sustaining a digital library requires surviving all types of change. This paper will include a behind-the-scenes look at situations we have faced and will continue to encounter, as well as a 'survival guide' for coping with change. By sharing our experiences and strategies, we hope to provide those planning new digital projects a glimpse at what they may face over time. Institutions with established projects may discover challenges and strategies they have not previously encountered and may be inspired to improve these coping methods.