The junction-spreader thermal resistance is an important part of the overall junction-ambient thermal resistance in electronic packages. Past research has provided theoretical models for contact thermal resistance between the thermal interface material (TIM) and the contacting rough solid surface. However, these models are based on steady-state assumptions and do not describe the evolution of the junction-spreader thermal resistance during the lifetime of an electronic package. This chapter presents a transient model for the junction-spreader thermal resistance based on classical theories for lubrication and surface wettability. This transient model provides a simple relationship for pressure-dependent junction-spreader thermal resistance and yields an optimum filler volume fraction for particle filled TIMs. An experimental approach developed in this chapter measures the pressure-dependence, as well as the spatial distribution of junction-spreader thermal resistance. The data agree reasonably well with the model predicting for the pressure-dependent junction-spreader thermal resistance. The theoretical and experimental approaches developed in this study are promising tools for thermal management and reliability engineering of electronic packaging.