An invasive fungal infection is a rare disease that can occur in otherwise healthy individuals. Fungi themselves are universal, and they are overall harmless organisms that cause at most a self-limiting disease in the general population. Immunocompromised individuals, whether iatrogenically, genetically, or acquired, present a group who are especially susceptible to a life-threatening disease from a normally innocuous pathogen. Fungi are normally inhaled and are cleared by pulmonary defense mechanisms in immunocompetent hosts. Invasion begins when these mechanisms fail in depressed immunity. Through bypassing of the pulmonary immune system, fungi can spread hematogenously. Fungal infections of the central nervous system are the most common extrapulmonary manifestation after fungal inhalation. Other risk factors of fungemia include prolonged indwelling catheters, maxillofacial infections, uncontrolled diabetes mellitus, systemic antibiotics, implanted neurosurgical devices, and intravenous drug abuse. Thus, other than direct inoculation via surgical complications or open trauma, central nervous system fungal infections are almost never primary.