Microbial and plant specialized metabolites, also known as natural products, are key mediators of microbe-microbe and host-microbe interactions and constitute a rich resource for drug development. In the past decade, genome mining has emerged as a prominent strategy for natural product discovery. Initially, such mining was performed on the basis of individual microbial genome sequences. Now, these efforts are being scaled up to fully genome-sequenced strain collections, pan-genomes of bacterial genera, and large sets of metagenome-assembled genomes from microbial communities. The Medema research group aims to play a leading role in these developments by developing and applying computational approaches to identify, classify, and prioritize specialized metabolite biosynthetic gene clusters and pathways and to connect them to specific molecules and microbiome-associated phenotypes. Moreover, we are extending the scope of genome mining from microbes to plants, which will allow more comprehensive interpretation of the chemical language between hosts and microbes in a microbiome setting.