The Cordyceps fungus occupied trending topics after being portrayed in the series “The Last of Us” as being capable of transforming human beings into “zombies.” In reality, the host of this species, Ophiocordyceps unilateralis, thankfully, are ants (Pappas and Vrioni, Emerg Infect Dis 30:595, 2024). However, climate change and the high rates of immunocompromised people around the world, especially in developing countries, bring to light alarming data about the increase in mycotic infections and the lack of effective treatments, especially in infections that affect the nervous system (Konkel, Environ Health Perspect 132:42001, 2024). In this chapter, we begin our discussion with a review of recent findings in neuroimmunology, exemplifying current advances in research into the physical and immunological barriers that surround the nervous system, once described as a structure provided with immunological privilege given by the absence of nervous system activity. Immune system and we will correlate these topics with the infection, diagnosis and treatment of fungal diseases in the central nervous system (CNS), especially in immunocompromised individuals, since the vast majority of fungi manifest themselves as opportunistic pathogens.