This chapter presents fundamental scientific tools as well as potential applications relevant to the emerging field of nanotechnology. In particular, understanding the behavior of molecularly thin lubricant films is essential for achieving durability and reliability in nanoscale devices, and the experimentation and theory for the physicochemical properties of ultrathin perfluoropolyether (PFPE) films are reviewed. A method for extracting spreading properties from the scanning microellipsometry (SME) for various PFPE/solid surface pairs and the theological characterization of PFPEs are examined at length. The interrelationships among SME spreading profiles, surface energy, rheology, and tribology, are discussed as well. Phenomenological theories, including stability analysis and microscale mass transfer, are introduced to interpret ultrathin PFPE film nanostructures qualitatively. In addition, rigorous simulation tools, including a lattice-based simple reactive sphere model, the off-lattice bead-spring Monte Carlo method, and molecular dynamics method, are examined. These tools may accurately describe the static and dynamic behaviors of PFPE films consistent with experimental findings and thus will be suitable for describing the fundamental mechanisms of film dewetting and rupture due to instability arising from nanoscale temperature and pressure inhomogeneities. Nanotribological applications, such as finding an optimal disk lubricant based on a molecule-level interaction of the lubricant with solid surfaces, will be explored.