IFN-gamma is released in the brain, not only during acute infectious diseases or immunological reactions, but also for extended periods of time after clearance of infectious virus and during viral latency. In this review, we focus on the role of IFN-gamma in the interaction between a neuron and a pathogen, that is, the role in implementation of microbial destruction, stasis or persistence, its potential neuroprotective or toxic effects, and how this cytokine may affect neuronal function and the behavior of an individual.