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Substance use disorder is a chronic, relapsing disease for which all those living with this mental health condition deserve access to safe, ethical, appropriate care and treatment. Drug diversion, a possible consequence of substance use disorder, puts nurses, patients, organizations, and the public at significant risk. A review of the literature indicates that controlled substance diversion prevention programs are essential to drug diversion prevention efforts, education is key to promoting a culture of safety and encouraging staff to speak up, and alternative-to-discipline approaches should be considered when managing personnel involved in actual drug diversion cases. Additional nursing-focused articles are needed to guide nurses and nurse leaders on this complex and challenging issue. This article outlines a drug diversion prevention program's development and implementation at a large academic medical center in the Midwest. Nursing involvement, leadership, and expertise are paramount to this program's prevention, detection, and response efforts.