Microbial sulfate reduction is subject to a thermodynamic limit arising from the micro-organisms' need to save energy for maintenance and growth, and this limit prevents the process from proceeding until the supply of electron donor or sulfate has been consumed, as would be expected from commonly applied kinetic theory. In pure culture experiments, acetotrophic sulfate reduction stops when the energy liberated by the reaction falls to ~33–43 kJ·(molSO42−)−1, and an overlapping range of 40–56 kJ·(molSO42−)−1 is observed where sulfate reduction has ceased in experiments with microbial consortia, as well as in nature, in lacustrine, marine, and aquifer sediments. These observations correspond to an energetic requirement of 33–47 kJ·(molSO42−)−1 calculated on the basis of the cellular physiology of sulfate reducers. In sediments underlying Lake Washington, USA, variation of pore-water chemistry with depth can be explained by a reactive transport model accounting for cellular energy conservation, whereas a model in which thermodynamics are neglected predicts an unrealistic pattern. Energy availability constitutes a primary, if commonly overlooked, control on the distribution and rate of microbial sulfate reduction in nature and helps resolve apparent contradictions observed in the laboratory and natural environment.