Stigma affects how we see and treat people living with mental health and/or substance use (MHSU) problems or illnesses. When it becomes embedded throughout the health-care system, it creates real barriers and harms for people trying to access quality care. But change is possible once we commit to dismantling such MHSU-related structural stigma and rebuilding our structures and systems to ensure equitable, effective, and quality care for all. The goal of this guide is to share knowledge about the key features of structural change and strategies and the considerations for making it happen — and to provide guidance to those interested in reducing MHSU-related structural stigma in their organizations.