The replacement of fossil and agricultural feedstocks with sustainable alternatives for the production of chemicals and fuels is a societal and environmental necessity. This challenge can be tackled by using inorganic or one-carbon compounds as electron donors for microbial CO2 fixation and bioproduction. Yet, considering the wide array of microbial electron donors, which are the best suited for bioindustry? Here, we propose criteria to evaluate these compounds, considering factors such as production methods, physicochemical properties, and microbial utilization. H2, CO, and formate emerge as the most promising electron donors as they can be produced electrochemically at high efficiency and, importantly, have reduction potentials low enough to directly reduce the cellular electron carriers. Still, further research towards the production and utilization of other electron donors — especially phosphite — might unlock the full potential of microbial CO2 fixation and bioproduction.