Primary care has changed in the past 40 years, and research performed within and by practice-based research networks (PBRN) needs to change to keep up with the current practice landscape. A key task for PBRNs is to connect with today’s stakeholders, not only the traditional physicians, providers, office staff, and patients, but health systems, insurance companies, and government agencies. In addition to one-time externally funded engagement efforts, PBRNs must develop and report on sustainable, long-term strategies. PBRNs are also demonstrating how they use classic practice-based research techniques of practice facilitation and electronic health record (EHR) data extraction and reporting in new and important research areas, such as studying the opioid epidemic. PBRNs are adapting and transforming along with primary care.