Species of the genus Trichoderma inhabit diverse environments and undergo a variety of interactions with different other organisms. Mycoparasitic Trichoderma species are successfully applied as bio-fungicides due to their lant-protecting abilities and they are prolific producers of secondary metabolites which comes along with an enrichment in secondary metabolism-associated genes in their genomes. The objective of this article is to review the secondary metabolites produced by Trichoderma spp. along with a comprehensive overview of their genomic content for genes and gene clusters being involved in secondary metabolite biosynthesis. We discuss the bioactivity of selected Trichoderma-derived secondary metabolites with a focus on their roles in the interactions of Trichoderma with plants and fungal preys and give an overview on methods for secondary metabolite profiling.