Stable isotopes serve as naturally occurring tracers that can provide much information about how chemical reactions proceed in nature, such as which reactants are consumed and at what temperature reactions occur. This chapter shows how multicomponent chemical reaction models can be adapted to account for the stable isotope fractionation of hydrogen, carbon, oxygen, and sulfur. In the modeling approach, solid mineral phases can be held in isotopic equilibrium with the aqueous fluid or be segregated from isotope exchange. In the latter case, the isotopic composition of minerals varies only in response to precipitation and dissolution reactions. A fully worked example calculation traces the dolomitization reaction of a limestone, computed assuming the minerals are segregated from isotope exchange.