Photons with a great many tunable physical properties have been profoundly engaged in research of brain science in all aspects for more than a hundred years. Taking advantage of highly developed incoherent light sources, coherent lasers and short-pulse lasers, innovative optical tools including both instrumentations and strategies have signi¯cantly boosted comprehensive research on neural science within a very short period. Right before China launches its Brain Project (Chinese version of BRAIN -Brain Research through Advancing Innovative Neurotechnologies) by the end of this year (2017), we are delighted to introduce to our readers a special issue on applications of bio-photonics in neuroscience and brain diseases.This special issue is intended to introduce 11 original research papers and review papers that cover applications including optogentics, Raman spectroscopy, stimulated Raman scattering microscopy, light sheet, laser speckle contrast imaging, super-resolution and other areas of brain research innovated by advanced optical tools.The blood-brain barrier (BBB) is a persistent challenge for brain drug delivery. Many physical, chemical and biological methods are able to open BBB, but all of them have their limitations. Eketerina Borisova et al. successfully developed an optical approach based on photodynamic therapy (PDT) to break this physical barrier to access the central nervous system of brain.1 In the other paper from Alexey and his colleagues, the researchers applied laser speckle contrast imaging (LSCI) and multi-scale entropy (MSE) to image the blood°ow dynamics in a label-free manner.2 This optical tool also exhibited excellent capabilities in evaluating the dynamics of permeability of BBB as opened by sound exposure.Biological tissues are highly scattering for photons. In contrast to X-ray, MRI, and PET, interrogating photons or treatment light wave cannot travel very deep into the tissue, especially for brain tissues that contain largely lipids. The short penetration depth is a long-standing issue for optical brain imaging, photodynamic therapy, and other clinical applications. Ting Li et al. simulated light penetration by tuning the laser wavelength, beam shape and beam diameter through innovative high-realistic 3D Monte Carlo modeling.3 Long-wavelength infrared laser and near infrared laser (> 800 nm) are typically chosen to study most of the tissue samples. The research team at Tsinghua University applied a 465-nm laser to invoke optical compound action potentials (OCAPs) successfully by manipulating laser pulse energy and pulse duration.4 To obtain complete 3D structure of whole mouse brain, Prof. Peng Fei and his team at Huazhong University of Science and Technology combined chemical tissue clearance and light-sheet°uorescent microscopy (LSFM) for high-speed imaging.5 With much reduced tissue scattering, the LSFM achieved four times better spatial resolution as well as superior imaging quality. Despite the di±culties of 3D volume imaging, the astrocyte and pyramidal neurons together with det...