The importance of nonfouling (bioadhesion-resistant) coatings of solid surfaces has been emerging in various fields ranging from biomedicine to shipbuilding. Although a large number of approaches to endow the solid surfaces with bioinertness have been reported, a thorough understanding of the mechanism underlying the bioinertness of surfaces at a molecular level has not been achieved. Self-assembled monolayers (SAMs) provide powerful platforms on which to systematically investigate the processes of adsorption and adhesion of biomolecules, because of the tunability of their surface chemical properties depending on terminal groups and well-defined structures. In this review, we introduce types of bioinert SAMs and focus especially on the SAMs of oligo(ethylene glycol)-terminated alkanethiols on gold surfaces (OEG-SAM), which have been the most investigated nonfouling monolayers. We survey works that elucidate the mecha-nism underlying the bioinertness of the nonfouling SAMs using experimental and theoretical techniques and summarize the present situation of this field. We also mention nonfouling polymer surfaces and discuss perspectives to bridge the findings of monolayers and polymers.