The extreme sensitivity of both reflected and transmitted polarized light to the micro-structure of studied object has attracted many researchers for exploring optical polarization as a tool for the studies of brain—the most complex organ in a vertebrate’s body. The polarization of light was used for the variety of applications starting from the fundamental studies of brain connectome (a map of the neural connections that creates the basis for functional neuroimaging at micro-, meso- and macro-scale) and moving towards the medical diagnosis and staging of the Alzheimer disease, fiber tracking of brain white matter for the delineation of brain tumor border, etc. Both partial and complete polarimetric techniques are widely used to assess the depolarization and polarization (i.e., retardance, dichroism) properties of brain tissue by measuring the phase shift and/or diattenuation of the probing light beam. In this chapter we discuss the optical properties of brain tissue, the basics of polarized light interaction with optically anisotropic complex scattering media, and demonstrate the examples of brain tissue case studies providing the perspectives of future clinical applications.