Engineering materials are commonly polycrystalline in nature and chemically inhomogeneous containing hetero-phases and interfaces. Because diffusion is ubiquitous in dissimilar phases and defects, it plays a vital role in the performance and reliability. During the last several decades, a synergism of the microstructural properties and chemical inhomogeniety with diffusion has been attempted to unify their apparently diverse behavior. We discuss the methodology and the thermodynamical analyses of the diffusion data needed to obtain this synergism quantitatively and illustrate it by the results obtained in a wide variety of materials, both metallic and non-metallic. Investigations carried out in pure polycrystalline metals have yielded grain boundary energies comparable to those directly measured. Furthermore, we discuss the role of solute segregation at grain boundaries and interfaces in alloys in altering diffusion. From the perturbations caused, the solute segregation parameters - the enthalpy and the entropy of binding - have been extracted and levels of solute concentrations estimated. Finally, it is shown that similar analyses when applied to complex materials, e.g. the Pb-Sn eutectic alloy, the Ni3Al intermetallic compound, and an Ag-ceramic system, also result in acceptable values of interface energies and segregation factors.