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Purpose of Review: The present review examines how targeted approaches to care, based on individual variability in patient characteristics, could be applied in the perioperative setting. Such an approach would enhance individualized risk assessment and allow for targeted preventive and therapeutic decision-making in patients at increased risk for adverse perioperative events., Recent Findings: Prior and current studies highlight valuable lessons on how future investigations attempting to link specific patient-related characteristics or treatment modalities with outcomes and adverse drug responses might be designed in the perioperative setting., Summary: Our review highlights the past, present, and future directions of perioperative precision medicine. Current evidence provides important lessons on how a specific patient and disease tailored approach can help perioperative physicians in delivering the most appropriate and safest perioperative care.