The National Association of School Nurses (NASN) developed the Framework for 21st Century School Nursing Practice to reflect current school nurse practice. The Framework of practice was introduced in June 2015, and feedback was requested and obtained from practicing school nurses in a variety of ways. The final version of the Framework is introduced in this article. This article updates (and replaces) the articles in the July 2015 NASN School Nurse related to the Framework. Central to the Framework is student-centered nursing care that occurs within the context of the students' family and school community. Surrounding the student, family, and school community are the nonhierarchical, overlapping key principles of Care Coordination, Leadership, Quality Improvement, and Community/Public Health.These principles are surrounded by the fifth principle, Standards of Practice, which is foundational for evidence-based and clinically competent quality care. Each of these principles is further defined by practice components. Suggestions are provided regarding how the Framework can be used in a variety of settings to articulate and prioritize school nursing practice. The ultimate goal is to provide a resource to guide school nurses in their practice to help students be healthy, safe, and ready to learn.