Fluorosis severely affects the quality of life of people causing metabolic and degenerative disorders. Its alarming upsurge in the recent years is a matter of deep concern and warrants intense research to completely eliminate this food and water borne ailment. Compelling evidence indicates that fluoride produces injury not only to the central nervous system but also to the immune system which is the first line of defense against xenobiotics. Studies have demonstrated that the intelligence of children and animals exposed to high levels of fluoride caused lowered learning ability and memory. Fluoride causes neuronal destruction and synaptic injury by free radical production and lipid peroxidation. Although limited information is available about immunotoxicity, it is hypothesized that fluoride affects cells of humoral and cell mediated immune responses. In addition, fluoride is reported to decrease white blood cell counts. Though there have been prospective studies in the past which elucidated various aspects of fluoride induced toxicity, the exact comprehensive understanding of the molecular and biochemical mechanisms of fluoride on the neuroimmunological processes is still a subject that needs clinical evaluation. Fluorosis is an endemic problem affecting the quality of life of millions in Saudi Arabia. However, only a few studies are conducted in this region. Owing to its alarming upsurge in recent years, it is important to design future studies to evaluate the neurotoxic and immunotoxic potential of fluoride exposure in humans.