Neuroinflammation demands a comprehensive appraisal in situ to gain in-depth knowledge on the roles of particular cells and molecules and their potential roles in therapy. Because of the lack of appropriate tools, direct visualization of cells has been poorly investigated up to the present. In this context, reporter mice expressing cell-specific fluorescent proteins, combined with multiphoton microscopy, provide a window into cellular processes in living animals. In addition, the ability to collect multiple fluorescent colors from the same sample makes in vivo microscopy uniquely useful for characterizing many parameters from the same area, supporting powerful correlative analyses. Here, we present an overview of the advantages and limitations of this approach, with the purpose of providing insight into the neuroinflammation field. We also provide a review of existing fluorescent mouse models and describe how these models have been used in studies of neuroinflammation. Finally, the potential for developing advanced genetic tools and imaging resources is discussed. ⃝C 2016 by John Wiley & Sons, Inc.