It had long been thought that the central nervous system was isolated from the immune system owing to the blood-brain barrier and that this organ was unable to mount an immune reaction of its own when challenged by invading pathogens. It is now clear that the immune system has a profound impact on the central nervous system, because immune molecules found in the blood stream are able to stimulate cells within the brain. Moreover, recent studies have demonstrated that cells within the central nervous system have the capacity to produce molecules of the innate immune system and that this organ is able to generate a proper immune reaction. This topic has been extensively studied in recent years, and it is becoming clear that the innate immune system is an important modulator of the fate of neurons. Indeed, the precise role(s) of the innate immune response in neurodegenerative diseases is currently under intensive debate. In this review paper, we present evidence either supporting or opposing a role for the innate immune response in these events. The mechanisms by which pathogens interact with the brain and whether such an interaction leads to neurodegenerative disorders are also discussed.