Interactions between surfaces are ubiquitous phenomena in living organisms. Nature has developed sophisticated strategies for lubricating these systems, increasing their efficiency and life span. This includes the use of water-based lubricants, such as saliva and synovial fluid. These fluids overcome the limitations of water as a lubricant by the presence of molecules such as proteins, lipids, and polysaccharides. Such molecules may alter surface interactions through different mechanisms. They can increase viscosity enabling fluid-film lubrication. Moreover, molecules adsorb on the surfaces providing mechanisms for boundary lubrication and preventing wear. The mentioned molecules have typical sizes in the nanometer range. Their interaction, as well as the interaction with the entrapping surfaces, takes place through forces in the range of nanonewtons. It is therefore not surprising that the investigation of these systems have been boosted by development of techniques such as scanning probe microscopies and the surface force apparatus which allow studying tribological processes at the nanoscale. Indeed, these approaches have generated an enormous amount of studies over the last years. The aim of this review is to perform a critical analysis of the current stage of this research, with a main focus on studies on synovial joints and the oral cavity.