The principles of combinatorial methodology are based on high-throughput properties measurements (HTPM) of multiple compositions in combinatorial libraries, and are recently being increasingly applied in materials research. Nevertheless, the authors' view is that the involvement of detailed but time-consuming investigation using transmission electron microscopy (TEM) should be an important part of combinatorial materials research. In this paper we present three examples from our combinatorial studies where the TEM investigation was essential in obtaining a detailed picture of microstructures and their relationship with the physical properties. In the study of microwave dielectrics such as BaTiO3-SrTiO3, TEM provides essential information on the type and distribution of defects in the deposited films. In the case of the wide-band semiconductor ZnO-MgO, the distribution and morphology of the phases were studied and related to the measured electronic properties. Study of the manganates LaMnO3-CaMnO3 with colossal magneto-resistive properties showed an anisotropic distribution of the structural domains and the morphology of the film. The distribution of the domains and the absence of epitaxial stresses found are essential in the interpretation of magnetic measurements.