Lubrication is critical to the success of total joint replacement. Despite significant progress in the understanding of molecular tribology for chemical systems, there is still a lack of a fundamental understanding of the lubrication mechanisms for joints and other biological systems. Currently, the most common solution to arthritis is total joint replacement. However, the biocompatibility of implanted materials poses a great challenge. In this work, friction between two surfaces covered by zwitterionic polymer brushes will be studied using both molecular simulation and experimental techniques. Three zwitterionic coatings will be studied and compared with PEG coatings. Through this work, insights will be gained into the origin of the friction between zwitterionic coatings at the molecular level and the relationship will be established between nano-scale friction and surface hydration. A fundamental understanding of the interfaces encountered in bionanotribology will guide the design of new biocompatible materials for applications in artificial joints and BioMEMS/NEMS.