Despite their diminutive size, microbes run our biosphere. They are the primary mediators of nearly every biogeochemical cycle, from carbon and nitrogen to methane and metals. Recent years have been a watershed for our understanding of microbes, largely due to advances in sequencing technologies. We have revealed previously unrecognized microbial diversity in every corner of our biosphere via these approaches, and have sequenced hundreds of microbial genomes. Our understanding of the metabolic and physiological activity, however, remains in its infancy. Despite the aforementioned advances, we have not made significant progress in growing (culturing) microbes, and to date over 99 percent of known microbial “species” continue to elude cultivation. In particular, our ability to interrogate their physiology while they exist as complex communities remains limited. This seminar aims to bring together experts in medical and environmental microbiology, materials science, chemistry and chemical biology, and environmental policy to discuss the state of the art in microbiology and their influence in our world (including human health), and to identify the most salient approaches to advancing our understanding of these critical yet enigmatic members of our biosphere.