Microorganisms alter minerals for a variety of reasons, including generation of more hospitable surroundings, extraction of nutrients, and sequestration of toxic substances. Minerals also may be altered passively by the products of microbial metabolism, such as production of acid. Microbes use minerals as sources and sinks of electrons for coupled oxidation-reduction reactions, and many of these reactions enable the release and capture of energy from unstable or metastable minerals. These processes can have dramatic results, such as the production of intensely acidic solutions during oxidation of sulfide minerals, or they can slowly and discretely transform minerals during weathering and diagenesis over geologic time. In either case, mineral sources of energy are transformed irreversibly by microbial metabolism. The purpose of this paper is to explore several central questions about microbial-mineral interactions, including the following: Under what conditions does a mineral represent an energy source for microbial metabolism? How can we evaluate the amount of energy available, and upon which factors does that energy supply depend most critically? How do we get from field and analytical data to an energy analysis for a natural system? This framework is illustrated with examples of known and postulated microbially mediated energy-yielding reactions involving minerals.