The intranasal pathway is a direct route of communication between the environment and the brain. This pathway is currently used for the delivery of several experimental therapeutic peptides and vaccines because it bypasses the blood brain barrier. It is also a route of entrance to the brain for several viruses and toxic substances. Airborne infectious, allergic and pollution agents are among the most common inflammatory factors which may affect brain function via the brain-nose interface. The inflammatory processes triggered in the upper respiratory tract by these agents are positioned to influence the immune response of the brain and therefore, influence its function and alter behavior. Several clinical and epidemiological studies find an association between inflammatory factors affecting the intranasal pathway and neurological disorders such as multiple sclerosis, Alzheimer and Parkinson diseases as well as mental disorders including anxiety and mood disorders. However the mechanisms of interaction between the immune response in the nasal epithelium and the brain are poorly understood. This article discusses current evidence about these mechanisms and associations with neurological and mental diseases.