Community health centers (CHCs) are important settings for research aimed at reducing health disparities. However, CHCs pose many challenges to research at patient, provider, and system levels. We summarized lessons learned from a multimethod, formative study to develop intervention strategies for improving colorectal cancer screening in CHCs, and make recommendations for future research. The call for research in "real world" settings such as CHCs must be matched with greater understanding of the challenges, as well as the resources to meet those challenges.