The United States has an opioid epidemic that requires efforts to help youths and families navigate complex challenges. Extension professionals are being called on to develop programs that equitably and effectively engage and serve audiences across racial and ethnic differences. To accomplish this, Extension professionals must understand the systemic and historic inequities that have shaped prevention and treatment initiatives within communities of color. Establishing culturally responsive practices is essential for building successful prevention programs. This article presents an overview of historical occurrences, challenges faced by communities of color, and recommendations for best practices.