On college campuses, a noteworthy shift is underway: alcohol consumption among students seems to be on the decline, marking a positive turn spurred by years of candid conversations, data-driven harm reduction initiatives, and targeted awareness efforts. Yet, amidst this progress, another trend persists—a rise in the self-reported use of other drugs among students. This increase takes on added gravity against the backdrop of the United States’ escalating overdose crisis, which has claimed more than a million lives since 2008. Despite the clear efficacy of harm reduction strategies in mitigating alcohol-related harm, institutions of higher education have been slow to adopt similar approaches for broader substance use issues on campus. This chapter delves into the pervasive influence of stigma on campus policies and cultures surrounding substance use. It underscores the need for a paradigm shift, advocating for a move away from moralistic judgments toward a compassionate, strengths-based approach centered on safety and recovery. By dismantling stigma and fostering empathy, campus stakeholders can promote lasting change. As campus professionals strive to improve the well-being of their communities, embracing a culture of empowerment emerges as a vital imperative in confronting the challenges of campus substance use.