Fungi can be found in virtually every habitat on earth. Over time, they evolved strategies to survive even the most challenging conditions, leading to their enormous diversity. For their survival in the habitat they have acquired the ability to produce a multitude of secondary metabolites, also named natural products. These unusual low-molecular-weight compounds exhibit a variety of effects, ranging from antimicrobial activity to protective compounds and information molecules for neighboring microorganisms. Through these effects, our recent data substantiate the hypothesis that secondary metabolites shape the composition of microbial consortia (microbiomes) by reducing or promoting the growth of certain microorganisms or changing their metabolic activity. Genetic analyses indicate that fungi have the potential to produce far more secondary metabolites than have been identified yet. Their encoding biosynthesis gene clusters remain silent under laboratory conditions and the ecological context is required for their activation. Therefore, we have initiated research on the activation of such silent gene clusters by microbial communication. Since then, many studies attempted to mimic naturally inducing conditions, e.g., by varying culture conditions, genetic manipulation of the producing organism, or co-culturing of multiple microorganisms. Elucidating the ecological roles of these compounds and the underlying triggers leading to their production is of major importance for our understanding of how microbial communities are shaped and how complex interactive networks can be formed with their profound influence on human health and the environment. Further, understanding the ecological trigger regulating the production of secondary metabolites will allow us to shed light on the pool of yet unidentified compounds in search for potential new antibiotics and other useful compounds.