© 2019 Elsevier Inc. The nursing profession is tasked with identifying and evaluating models of care with potential to add value to health care delivery. In consideration of this goal, we describe the Clinical Nurse Leader (CNL) initiative and the activities of a national-level CNL research collaborative. The CNL initiative, launched by the American Association of Colleges of Nursing in collaboration with education and healthcare leaders, has delineated CNL education curriculum and practice competencies, and fostered the creation of academic-practice-policy partnerships to pilot CNL integration into frontline nursing care delivery. The partnership has evolved into an Agency for Healthcare Research and Quality affiliate practice-based research network, the CNL Research Collaborative, which links research, policy, education, and practice stakeholders to advance the CNL evidence base. We summarize foundational CNLRC research to explain CNL practice, quantify CNL effectiveness, and bring clarity to how CNLs can be implemented to consistently influence care, quality, and safety.