Natural products have been, without question, the most prolific source of all medicines, especially antibiotics. Genome sequencing has revealed that our knowledge of natural product structure and function is astonishingly incomplete. Therefore, exploration of uncharted natural product chemical space will undoubtedly lead to improved, and entirely new, medicines. Against this backdrop, our group focuses on elucidating the biosynthesis, structure, and function of natural products. This talk will highlight our recent advances in genomics-enabled natural product discovery while covering a few case studies in enzymatic biosynthesis that could be exploited to introduce new drug leads.