It was once believed that the brain was an “immune-privileged” site protected from the immune response. However, it is clear that a number of common pathogens such as malaria and Toxoplasma gondii can invade the brain and provoke cerebral inflammation. Furthermore, inflammation worsens diseases of the brain such as Alzheimer’s disease and stroke. Thus, it is apparent that cells in the brain and central nervous system are capable of initiating and propagating inflammatory responses. Moreover, there is a growing body of evidence that systemic and/or peripheral inflammation may affect brain and central nervous system physiology, with immune cells able to actively invade the brain from the periphery. Our work uses models of infection to address the effects of acute, local and systemic inflammation on the nervous system and susceptibility to brain disease. In addition we address the molecular and cellular pathways that promote inflammation in the brain.