Thermally-grown oxide scales on high temperature alloys can provide oxidation protection if they are slow-growing, dense and adherent to the substrate. The factors affecting the integrity of the metal/oxide interface during dynamic oxidation processes are complex and include interfacial segregation, interface morphology, near-interface substrate properties, as well as the development of stresses in the growing oxide scale. Minor additions of reactive elements (RE) to the base metal have been shown to improve the oxidation performance of many high temperature materials. Studies on a variety of alloys have shown that the presence of reactive elements in the alloy affects segregation processes at both the metal/oxide and oxide/oxide interfaces. Whereas segregation to the metal/oxide interface can affect the scale adherence, segregation to the oxide/oxide interfaces in RE-containing systems has been proposed to result in changes in transport mechanisms as well as changes in the scale microstructure itself. High spatial resolution analytical electron microscopy techniques have been used to provide information on the microstructure and microchemistry of the scale and the metal/oxide and oxide/oxide interfaces. In general, in systems which exhibit improved oxidation performance, a consistent set of interfacial segregation phenomena and microstructural features were observed. Examples will be shown from a variety of nickel- and iron-based alumina formers. These kinds of studies, combined with traditional scanning electron microscopy studies of oxide scales can lead to the development of a more complete link between RE doping, interfacial segregation, interfacial/scale microstructure, and oxidation performance.