The selection for multidrug-resistant infectious pathogens and their global distribution is fuelling the need for new antibiotics and their alternatives. Natural products from bacteria and fungi are the traditional sources for our antibiotics used in human and animal health, however, the antibiotic discovery and development sector has largely pivoted away from these molecules towards synthetic compounds over the past three decades with poor results. The move away from natural products in antibiotic discovery was prompted, among other things, by the frequent rediscovery of known scaffolds with a resulting lack of new chemical diversity, the chemical complexity and low yields of many natural products that is incompatible with modern high throughput discovery, the challenges of identifying new biological sources of compounds, and a focus on single-agent broad spectrum candidates. The 21st Century genomic era offers creative solutions to many of these drawbacks. In this presentation, I will cover our efforts to build a library of producers of natural products and the use of modern genomic technologies to identify new and rare compound scaffolds.