Fungal primary pathogenicity on vertebrates is here described as a deliberate strategy where the host plays a role in increasing the species fitness. Opportunism is defined as coincidental survival of an individual strain in host tissue using properties that are designed for life in an entirely different habitat. In that case the host's infection control is largely based on innate immunity, and the etiologic agent is not transmitted after infection, and thus fungal evolution is not possible. Primary pathogens encompass two types, depending on their mode of transmission. Environmental pathogens have a double life cycle, and tend to become enzootic, adapted to a preferred host in a particular habitat. In contrast, pathogens that have a host-to-host transmission pattern are prone to shift to a neighboring, immunologically naive host, potentially leading to epidemics. Beyond these prototypical life cycles, some environmental fungi are able to make large leaps between dissimilar hosts/habitats, probably due to similarity of key factors enabling survival in an entirely different niche, and thus allowing a change from opportunistic to primary pathogenicity. Mostly, such factors seem to be associated with extremotolerance.