This chapter presents a review of significant experimental and theoretical aspects of nanotribology. Innovative experimental techniques including surface force apparatus (SFA) and atomic force and friction force microscopes (AFM/FFM), and molecular dynamics (MD) computer simulations are used to study the interaction of materials ranging from atomic scales to microscales. First, the chapter talks about SFA experiments used to study adhesion and friction of a molecularly thick liquid film confined between two smooth surfaces. Next, the chapter describes two commercial AFM/FFMs commonly used for measurements of nanotribological and nanomechanical properties ranging from micro- to atomic scales. Finally, the chapter presents an overview of MD simulation modeling and selected results dealing with various friction, wear, and indentation studies.