Isotopic information determined by mass spectrometry can be used in a wide variety of applications. Broadly speaking these could be classified as "passive" applications, meaning that they use naturally occurring isotopic information, and "active" applications, meaning that the isotopic distributions are manipulated in some way. The classic passive application is the determination of chemical composition by comparing observed isotopic patterns of molecules to theoretically calculated isotopic patterns. Active applications include isotope exchange experiments of a variety of types, as well as isotope labeling in tracing studies and to provide references for quantitation. Regardless of the type of application considered, the problem of theoretical calculation of isotopic patterns almost invariably arises. This chapter reviews a number of application examples and computational approaches for isotopic studies in mass spectrometry.