The misuse of prescription opioids is a major public health problem in the United States, Canada, Australia and other parts of the developed world. Methods to quantify dimensions of the risk environment in relation to drug usage and law enforcement that are both structural and spatial, draw geography into traditional public health research even though there has been limited attempt to address the prescription opioid misuse problem from a geographic perspective. We discuss how geographic technologies can be utilized to study the landscape of prescription opioids and similar drugs, and target appropriate health services interventions. We use examples drawn from various jurisdictions to present our case and highlight through these examples how a geospatial perspective can help support research on prescription opioid misuse. The prescription drug misuse landscape can be studied through examination of the domains of demand, supply, harms and harm reduction. We discuss how each of these domains can benefit from a local geographic perspective, and subsequent geographic exploration and analyses.