In summary, the novel in vivo skull optical clearing technique provides an optical window for cortical observation without craniotomy. Over the past decades, with the development of technique, there are a variety of skull optical clearing windows available, each with its own characteristics. Through the skull optical clearing window, various modern optical imaging techniques have been used to noninvasively monitor neurovascular information. Up to now, the skull optical clearing window holds the advantages of high resolution, large scale, long-term observation, and is compatible with immediate observation, therefore has great potential in the research of brain science and related diseases.