Practice-based research networks (PBRNs) have developed a grounded approach to conducting practice-relevant and translational research in community practice settings. Seismic shifts in the healthcare landscape are shaping PBRNs that work across organizational and institutional margins to address complex problems. Praxis-based research networks combine PBRN knowledge generation with multi-stakeholder learning, experimentation, and practical knowledge application. The catalytic processes in praxis-based research networks are cycles of action and reflection based on experience, observation, conceptualization, and experimentation by network members and partners. To facilitate co-learning and solution-building, these networks have a flexible architecture that allows pragmatic inclusion of stakeholders based on demands of the problem and the needs of the network. Praxis-based research networks represent an evolving trend that combines the core values of PBRNs with new opportunities for relevance, rigor, and broad participation.