Carbon dioxide (CO2) accumulation in the environment, due to various thermochemical activities, is the primary reason for drastic global climatic changes. For dealing with the large CO2 volume with low concentration, bioreduction to various valuable products seems a viable option. Certain factors including microbes, electron donors, and their thermodynamic and kinetic behavior are critical for this process. However, there is very rare literature available focusing on these aspects. In this review, a systematic classification of electron donors has been presented to better understand their role in CO2 bioreduction (C2R). A thermodynamic framework has been discussed to analyze the effect of abundantly available electron donors on the thermodynamics of C2R. The effect of the electron donors’ phase on the kinetics of C2R has been elucidated using classical two-film theory. Hydrogenotrophic syntrophic C2R has been presented as a special case.