Abstract.SignificanceSkin is the largest organ and also the first barrier of body. Skin diseases are common, and cutaneous microcirculation is relative to various diseases. Researchers attempt to develop novel imaging techniques to obtain the complex structure, components, and functions of skin. Modern optical techniques provide a powerful tool with non-invasiveness, but the imaging performance suffers from the turbid character of skin.In vivoskin optical clearing technique has been proposed to reduce tissue scattering and enhance penetration depth of light and became a hot topic of research.AimThe aim of this review is to provide a comprehensive overview of recent development ofin vivoskin optical clearing methods, howin vivoskin optical clearing enhances imaging performance, and its applications in study and light therapy of various diseases.ApproachBased on the references published over the last decade, the important milestones on the mechanism, methods, and its fundamental and clinical applications ofin vivoskin optical clearing technique are provided.ResultsWith the deepening understanding of skin optical clearing mechanisms, efficientin vivoskin optical clearing methods were constantly screened out. These methods have been combined with various optical imaging techniques to improve imaging performances and acquire deeper and finer skin-related information. In addition,in vivoskin optical clearing technique has been widely applied in assisting study of diseases as well as achieving safe, high-efficiency light-induced therapy.ConclusionsIn the last decade,in vivoskin optical clearing technique has developed rapidly and played an important role in skin-related studies.