Monosodium glutamate (MSG) is a worldwide flavor enhancer. Despite controversy surrounding the safety of MSG, it is still consumed in large amounts. This review provides a better understanding of the molecular mechanism of MSG induced neurotoxicity including the different ways of glutamate regulation in brain and umami taste signaling pathway. In addition, this review summarizes the history of MSG discovery and synthesis, products and natural food containing MSG, details of MSG safety and toxicity with limited allowed amounts that can be used according to different organizations opinion. Finally, this review enumerates the different MSG studies in both animals and humans in the last 20 years.