© 2015 Wiley Periodicals, Inc.. Background Surgical resection with negative margins remains the standard of care for high-risk cutaneous squamous cell carcinoma (SCC). However, surgical management is often limited by poor intraoperative tumor visualization and inability to detect occult nodal metastasis. The inability to intraoperatively detect microscopic disease can lead to additional surgery, tumor recurrence, and decreased survival. Methods A comprehensive literature review was conducted to identify studies incorporating optical imaging technology in the management of cutaneous SCC (January 1, 2000-December 1, 2014). Results Several innovative optical imaging techniques, Raman spectroscopy, confocal microscopy, and fluorescence imaging, have been developed for intraoperative surgical guidance. Fifty-seven studies review the ability of these techniques to improve cutaneous SCC localization at the gross and microscopic level. Conclusion Significant advances have been achieved with real-time optical imaging strategies for intraoperative cutaneous SCC margin assessment and tumor detection. Optical imaging holds promise in improving the percentage of negative surgical margins and in the early detection of micrometastatic disease.