Fermentation is a type of metabolism carried out by organisms in environments without oxygen. Despite being studied for over 185 years, the diversity and complexity of this metabolism are just now becoming clear. Our review starts with the definition of fermentation, which has evolved over the years and which we help further refine. We then examine the range of organisms that carry out fermentation and their traits. Over ¼ of all prokaryotes are fermentative, use more than 40 substrates, and release more than 50 metabolic end products. These insights come from studies analyzing records of thousands of organisms. Next, our review examines the complexity of fermentation at the biochemical level. We map out pathways of glucose fermentation in unprecedented detail, covering over 120 biochemical reactions. We also review recent studies coupling genomics and enzymology to reveal new pathways and enzymes. Our review concludes with practical applications for agriculture, human health, and industry. All these areas depend on fermentation and could be improved through manipulating fermentative microbes and enzymes. We discuss potential approaches for manipulation, including genetic engineering, electrofermentation, probiotics, and enzyme inhibitors. We hope our review underscores the importance of fermentation research and stimulates the next 185 years of study.