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Over the last billion years, the fungal kingdom has diversified to over 10 million species with over 95% still undescribed. Beyond the well-known macroscopic mushrooms and microscopic yeast, fungi are heterotrophs that feed on almost any organic carbon, recycling nutrients through decay of dead plants and animals and sequestering carbon into the Earth’s ecosystems. Human directed applications of fungi extend from yeast responsible for leavened bread, alcoholic beverages, and biofuels to pharmaceuticals, including antibiotics and psychoactive compounds. Conversely fungal infections pose risks to ecosystems ranging from crops to wildlife to humans, driven in part by human and animal movement and potentially accelerating with climate change. Genomic surveys are expanding our knowledge of the true biodiversity of the fungal kingdom while genome editing tools make it possible to imagine harnessing these organisms to fuel the bioeconomy. Here, we explore the fungal threats facing civilization and opportunities to harness fungi to combat these threats.