Nonhost resistance (NHR) is a plant immune response that prevents many microorganisms in the plant's environment from pathogenicity against the plant. Since successful pathogens have adapted to overcome the immune systems of their host, the durable nature of NHR has potential in the management of plant disease. At present, there is genetic and molecular evidence that the underlying molecular mechanisms of NHR are similar to the plant immune responses that occur in host plants following infection by adapted pathogens. We consider that the molecular basis of NHR is multilayered, conferred by physicochemical barriers and defense responses that are induced following molecular recognition events. Moreover, the relative contribution of each component may depend on evolutionary distances between host and nonhost plants of given pathogen species. This mini-review has focused on the current knowledge of plant NHR, especially the recognition of non-adapted pathogens by nonhost plants at the cellular level. Recent gains in understanding the roles of plasma membrane-localized pattern-recognition receptors (PRRs) and the cytoplasmic nucleotide-binding leucine-rich repeat receptors (NLRs) associated with these processes, as well as the genes involved, are summarized. Finally, we provide a theoretical perspective on the durability of receptor-mediated NHR and its practical potential as an innovative strategy for crop protection against pathogens.