The science of learning and development demonstrates that when young people maintain positive school-based relationships, their learning and well-being is supported and enhanced. This brief elevates the practices and approaches that secondary school educators and staff can use to put relationships and caring at the center of their practice. It describes personalization tools and practices that can cultivate positive student-teacher relationships and empathy-building. It also highlights approaches that school adults can use to promote a sense of safety and belonging, including practices that foster community-building, restorative approaches to conflict resolution, identity safety, student agency, and social and emotional wellness. The practices in this brief are vital to cultivating personalized and trustful relationships. When coupled with the school-level structures described in the companion brief, "Cultivating Relationships in Secondary Schools: Structures That Matter," these relationship-centered practices can optimize student learning, well-being, and agency.