Despite the notable successes in producing synthetic inorganic materials and molecules that reduce CO₂, nature has provided catalytically efficient enzymes capable of the same feat at ambient temperature and pressure. Whilst many factors contribute to their high efficiency, electrochemical methods have highlighted the importance of metal–cofactor redox potential upon electron transport and transfer in many reactions. The fact that many enzymes are electrochemically accessible opens the door to the development of catalytic hybrid bio-electrochemical devices. Myriad approaches have been taken in order to harness enzymes within high-efficiency, high-specificity bio-electrochemical (BEC) CO₂ reducing devices. Whilst many enzymes are only able to indirectly interact with an electrode via reducing equivalents, direct electron transfer (DET) has recently been shown to be highly effective with several metal-containing enzymes. A wide variety of dehydrogenase enzymes have been incorporated into BEC CO₂ reducing systems to generate products including carbon monoxide, formate and ethanol. Microorganisms provide a natural environment within which enzymes are generated and can function effectively, and exhibit functional stability over long periods of time. Promising results have been achieved using electrochemically generated H₂ as a reducing equivalent, and genetic engineering is also now providing a remarkable approach for selecting and optimising preferred CO₂ reduction products. Many bio-inspired approaches to CO₂ reduction have also been developed, and in this chapter BEC and inorganic examples inspired by photosynthesis are examined. High-performance inorganic systems have achieved stable reduction of CO₂ to CO over 18 h with activity of over 100 μmol h⁻¹ cm⁻¹, around 90% faradaic efficiency and a solar to product efficiency of 6.5%.