The development of a bio-refinery industry based on liquid fuels is presumably key to successful replacement of fossil fuels and a reduction of carbon dioxide (CO2) emissions. Ethanol and longer-chain alcohols are supposed to play a key role since they are relatively easy to produce, using microorganisms as whole-cell biocatalysts. Alcohols may be produced from lignocellulose-derived biomass or from synthesis gas (hydrogen, H2; CO2, carbon monoxide, CO). In anaerobes, common pathways involve the reduction of the intermediate acetyl-CoA with NAD(P)H by aldehyde (ALDH) and alcohol dehydrogenases (ADH). Alternatively, alcohols may be produced by the direct reduction of externally added or intermediately produced organic acids with reduced ferredoxin (Fdred). The key enzyme catalyzing this thermodynamically difficult reaction is aldehyde:ferredoxin oxidoreductase (AOR), an oxygen sensitive protein present in some anaerobic bacteria and archaea. Here, we present increasing evidence for the importance of the AOR-ADH pathway in alcohol producing anaerobes. AOR heavily depends on compounds with a low redox potential, and reactions potentially coupled to the pathway are discussed. The putative ancient AOR-ADH pathway may be relatively widespread among anaerobes, and it may play an important role in a sustainable bioenergy concept via the reduction of organic acids to their corresponding alcohols.