There is growing demand for new bioactive compounds and biologicals for the pharmaceutical, agro- and food industries. Plant-associated microbes present an attractive and promising source to this end, but are nearly unexploited. Therefore, bioprospecting of plant microbiomes is gaining more and more attention. Due to their highly specialized and co-evolved genetic pool, plant microbiomes host a rich secondary metabolism. This article highlights the potential detection and use of secondary metabolites and enzymes derived from plant-associated microorganisms in biotechnology. As an example we summarize the findings from the moss microbiome with special focus on the genus Sphagnum and its biotechnological potential for the discovery of novel microorganisms and bioactive molecules. The selected examples illustrate unique and yet untapped properties of plant-associated microbiomes, which are an immense treasure box for future research.