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Protection motivation theory (PMT) is one of the most commonly used theories to examine information security behaviors. Our systematic review of the application of PMT in information systems (IS) security and the comparison with its application for decades in psychology identified five categories of important issues that have not yet been examined in IS security research. Discussing these issues in terms of why they are relevant and important for IS security, and to what extent IS research has not considered them, offers new research opportunities associated with the study of PMT and IS security threats. We suggest how future studies can approach each of the open issues to provide a new road map for quantitative and qualitative IS scholars.