Investigators for multisite research studies conducted in practice-based research networks face numerous challenges associated with Institutional Review Boards (IRBs) and human subjects protection. The American Academy of Family Physicians National Research Network (AAFP NRN) has adopted strategies to deal with some of these challenges, including creating an open, honest relationship with the new American Academy of Family Physicians Institutional Review Board (AAFP IRB); creating procedures for members who are not required to report to a local IRB; handling most of the IRB application submission and tracking tasks for our members who must submit applications to local IRBs; and working with the AAFP IRB to make required human subjects training relevant to our practices. However, these are only temporary solutions. It is time to begin working toward a permanent solution. As such, the AAFP, the AAFP NRN, and the AAFP IRB have begun discussing the possibility of adopting an alternative model of central IRB review, which would facilitate practice-based research in family medicine and which would encourage rather than discourage family medicine practices to participate in research studies that will further the discipline.