Biomass and other carbonaceous materials can be gasified to produce syngas with high concentrations of CO and H₂. Feedstock materials include wood, dedicated energy crops, grain wastes, manufacturing or municipal wastes, natural gas, petroleum and chemical wastes, lignin, coal and tires. Syngas fermentation converts CO and H₂ to alcohols and organic acids and uses concepts applicable in fermentation of gas phase substrates. The growth of chemoautotrophic microbes produces a wide range of chemicals from the enzyme platform of native organisms. In this review paper, the Wood–Ljungdahl biochemical pathway used by chemoautotrophs is described including balanced reactions, reaction sites physically located within the cell and cell mechanisms for energy conservation that govern production. Important concepts discussed include gas solubility, mass transfer, thermodynamics of enzyme-catalyzed reactions, electrochemistry and cellular electron carriers and fermentation kinetics. Potential applications of these concepts include acid and alcohol production, hydrogen generation and conversion of methane to liquids or hydrogen.