Despite recent advances in perforator flap reconstruction, there can be significant variability in vessel size and location. Although pre-operative evaluation may provide valuable information, real-time intraoperative methods have the potential to provide the greatest benefit. Our laboratory has developed the Fluorescence-Assisted Resection and Exploration (FLARE™) near-infrared (NIR) fluorescence imaging system for visualizing, intraoperatively, details of the underlying vasculature. The FLARE™ system uses indocyanine green, a safe and reliable NIR fluorophore already FDA-approved for other indications. The system has been optimized in large animal models for the identification of perforator size, location, and perfusion, and has also been translated to the clinic for use during breast reconstruction after mastectomy. In this paper, we review our pre-clinical and clinical data, as well as literature describing the use of similar NIR fluorescence imaging systems in plastic and reconstructive surgery.