Prescription drug diversion is a significant $25 billion-a-year problem in the US. Diversion can occur at any stage of the medicine delivery process, from manufacturing to the patient. Common diversion methods include illegal selling by doctors/pharmacists, “doctor shopping,” theft/forgery of prescriptions, and burglaries/thefts. Emerging diversion methods include theft by healthcare workers, fraud involving insurance, and theft from medicine cabinets. The main sources of diverted medications are at the practitioner-patient level, such as through “doctor shopping” and friends/family sharing prescriptions. Diversion from healthcare settings like hospitals accounts for a smaller proportion, though the exact extent is difficult to quantify. Some diversion occurs through theft from pharmacies, manufacturers, and supply chain points, but this makes up a relatively small percentage. Healthcare providers who engage in drug diversion have been linked to infectious disease outbreaks in hospitals, exposing patients to pathogens like hepatitis C. Intelligent systems and machine learning can help rapidly detect diversion anomalies. Comprehensive solutions are needed, including policy reforms, communication strategies, and a public health approach.