Fluorescence-guided surgery is evolving as a paradigm that could bring different contrast mechanisms into the surgical setting. The implementation of indocyanine green fluorescence for vessel perfusion imaging is now already a widespread commercial/clinical success,1 and the emergence of other probes, which could offer molecular-level information, is showing promise.2 One of the major problems to solve within this paradigm is that for real-time imaging, the traditional radiologic approach of window and level adjustment to maximize the display contrast is not feasible quickly, and automated display optimization methods are necessary. This issue is recently compounded by the increasing use of advanced imaging systems that digitize the image information into bit-depths significantly higher than 8 bits, thereby producing images with large dynamic ranges of luminance. Most imaging use linear display; however, ultrasound imaging is an analogous video-rate modality that regularly employs log-compression of the images.3 Fluorescence images can be acquired with camera bit-depths of 12 to 16 bits or higher, yet mainstream displays continue to use 8 bits per channel. Fluorescence imaging display quality is a mixture of many features, and the detected intensity at the camera can unfortunately easily vary by orders of magnitude. To compensate for undesirable background signals from tissue, nonlinear components, such as camera filters and noise, many systems have shifted to high dynamic range cameras, so that simple removal or a threshold can be applied to remove the background.4 This can work well and, in practice, may be the most practical way to proceed; however, as dynamic range has expanded, the potential value of image compression becomes more important. This value is obviously critical in areas where the real-time video stream is guiding the resection for tissue, such as with aminolevulinic acid for protoporphyrin IX fluorescence imaging5 or with newer classes of molecular probes.2 Logarithmic mapping of high dynamic range images, on the other hand, has been explored in detail6 as an automatic, fast, high-quality tone-mapping method to improve the quality of image display on devices with limited dynamic range. Logarithmic mapping has also found use in audio-level compression and is an established step in image preprocessing on ultrasound scanners3 and flow cytometers.7 In this paper, the concept of optimized logarithmic compression for fluorescence intensity images used in surgical guidance is presented and explored.