The ultimate outcome of this work is to support students, families, and educators (includes all school members who collectively support students) during the transitions back to school during and following the global pandemic in a manner that prioritizes their health and safety, social and emotional needs, and behavioral and academic growth. This guide describes the use of a multi-tiered systems of support (MTSS) framework, like positive behavioral interventions and supports (PBIS), to restart classrooms and schools in a manner that all students, families, and educators are supported effectively, efficiently, and relevantly. It provides a set of considerations for experienced leadership teams to enhance, adjust, or adapt state, district, school, and classroom action plans to meet the current context. Specifically, it offers recommendations for: (1) state leaders as they enhance their state-wide action plan to include a comprehensive plan for returning to school during a significant public health crisis; (2) district leaders as they enhance their district-wide action plan to include a comprehensive plan for returning to school during a significant public health crisis; (3) school leaders as they prepare to re-open school (in person and/or remotely) in the fall; and (4) educators as they develop and implement supports for students in their (in-person or remote) classrooms, groups, and other settings. [This report was co-produced by the National Integrated Multi-Tiered Systems of Support (I-MTSS) Research Network and the Lead for Literacy Center.]