Human-associated microbes are the source of many bioactive microbial products (proteins and metabolites) that play key functions both in human host pathways and in microbe-microbe interactions. Culture-independent studies now provide an accelerated means of exploring novel bioactives in the human microbiome; however, intriguingly, a substantial fraction of the microbial metagenome cannot be mapped to annotated genes or isolate genomes and is thus of unknown function. Meta'omic approaches, including metagenomic sequencing, metatranscriptomics, metabolomics, and integration of multiple assay types, represent an opportunity to efficiently explore this large pool of potential therapeutics. In combination with appropriate follow-up validation, high-throughput culture-independent assays can be combined with computational approaches to identify and characterize novel and biologically interesting microbial products. Here we briefly review the state of microbial product identification and characterization and discuss possible next steps to catalog and leverage the large uncharted fraction of the microbial metagenome.