Facing the urgent need to reduce the input of agrochemicals, in recent years, the ecological relationships between plants and their associated microorganisms have been increasingly considered as an essential tool for improving crop production. New findings and data have been accumulated showing that the application of fungi can go beyond the specific role that has been traditionally assigned to the species, employed in integrated pest management as entomopathogens or mycoparasites, and that strains combining both aptitudes can be identified and possibly used as multipurpose biocontrol agents. Mainly considered for their antagonistic relationships with plant pathogenic fungi, species in the genus Talaromyces have been more and more widely reported as insect associates in investigations carried out in various agricultural and non-agricultural contexts. Out of a total of over 170 species currently accepted in this genus, so far, 27 have been found to have an association with insects from 9 orders, with an evident increasing trend. The nature of their mutualistic and antagonistic relationships with insects, and their ability to synthesize bioactive compounds possibly involved in the expression of the latter kind of interactions, are analyzed in this paper with reference to the ecological impact and applicative perspectives in crop protection.