This brief from the Learning Policy Institute highlights the importance of positive school-based relationships in supporting and enhancing students’ learning and well-being, as demonstrated by the science of learning and development. It outlines effective practices that secondary school educators and staff can use to center relationships and care in their teaching. These include personalization tools and strategies for building strong teacher–student relationships, promoting empathy, and promoting safety and belonging. The brief also discusses approaches that encourage community-building, restorative conflict resolution, identity safety, student agency, and social-emotional wellness. These relationship-centered practices are essential for cultivating trustful, personalized connections that support deeper learning. When combined with the school-level structures outlined in the companion brief, Cultivating Relationships in Secondary Schools: Structures That Matter, these practices can maximize student engagement, well-being, and agency. This brief is valuable for educators, school leaders, and policymakers committed to creating supportive, equitable learning environments.