We discuss informatics-based challenges of constructing large-scale collaborative networks for healthcare research and analysis from rural community health centers. These types of networks provide data access and analytic insights across multiple heterogeneous health centers for both healthcare professionals and biomedical researchers. Challenges fall into three general categories: data access, data integration, and technical infrastructure. Data access issues arise in balancing patient privacy, security, and utility; data integration issues persist from each site independently operating its desired electronic medical record; technical infrastructure challenges include creating an analysis and reporting hub capable of scaling across a large collaborative network. Other challenges, such as the difficulty of site recruitment, are important to discuss, but cannot be solved directly through informatics alone. We discuss these challenges and their potential solutions in the context of our implementation of the Kentucky Diabetes and Obesity Collaborative (KDOC). KDOC is a network of Federally-Qualified Community Health Centers (FQHCs) that established a collaborative infrastructure for research and analysis of obesity and diabetes in rural and under-served communities.