Given that many fundamental questions in neuroscience are still open, it seems pertinent to explore whether the brain might use other physical modalities than the ones that have been discovered so far. In particular it is well established that neurons can emit photons, which prompts the question whether these biophotons could serve as signals between neurons, in addition to the well-known electro-chemical signals. For such communication to be targeted, the photons would need to travel in waveguides. Here we show, based on detailed theoretical modeling, that myelinated axons could serve as photonic waveguides, taking into account realistic optical imperfections. We propose experiments, both in vivo and in vitro, to test our hypothesis. We discuss the implications of our results, including the question whether photons could mediate long-range quantum entanglement in the brain.The human brain is a dynamic physical system of unparalleled complexity. While neuroscience has made great strides, many fundamental questions are still unanswered 1 , including the processes underlying memory formation 2 , the working principle of anesthesia 3 , and-most fundamentally-the generation of conscious experience 4-6 . It therefore seems pertinent to explore whether the brain might generate, transmit and store information using other physical modalities than the ones that have been discovered so far.In the present work we focus on the question whether biophotons could serve as a supplementary information carrier in the brain in addition to the well established electro-chemical signals. Biophotons are the quanta of light spanning the near-UV to near-IR frequency range. They are produced mostly by electronically excited molecular species in a variety of oxidative metabolic processes 7,8 in cells. They may play a role in cell to cell communication 7,9 , and have been observed in many organisms, including humans, and in different parts of the body, including the brain [10][11][12][13][14][15] . Photons in the brain could serve as ideal candidates for information transfer. They travel tens of millions of times faster than a typical electrical neural signal and are not prone to thermal noise at body temperature owing to their relatively high energies. It is conceivable that evolution might have found a way to utilize these precious high-energy resources for information transfer, even if they were just the by-products of metabolism to begin with. Most of the required molecular machinery seems to exist in living cells such as neurons 16 . Mitochondrial respiration 17,18 or lipid oxidation 19 could serve as sources, and centrosomes 20 or chromophores in the mitochondria 21 could serve as detectors. However, one crucial element for optical communication is not well established, namely the existence of physical links to connect all of these spatially separated agents in a selective way. The only viable way to achieve targeted optical communication in the dense and (seemingly) disordered brain environment is for the photons to travel in wavegu...