Recent experimental and theoretical findings of the effect of bulk properties, conductance, surface structure, and point defects in energy dissipation in various systems, including metals, semiconductors, quasicrystals, two-dimensional sheets, and organic molecular films is reported. A host of new phenomena, including friction anisotropy, superlubricity, and velocity dependence, have been uncovered and studied. In these experiments, the probe is brought into contact with an electron transparent sample and the interface is imaged in the TEM during contact while the probe simultaneously measures electrical (STM) or mechanical signals. In situ TEM techniques have already made it possible to directly measure electrical and mechanical properties of gold contacts, including atomic-sized contacts that exhibit quantized conductance steps associated with atomic rearrangements and high-resolution visualization of the deformation of nm-sized gold interfaces via slip and twinning.