Plant non-host resistance is the most common form of disease resistance exhibited by plant against the majority of potentially pathogenic microorganisms. The broad spectrum and durable resistance of non-host resistance suggests that plant non-host resistance has a significantly agricultural application, however, it's molecular mechanism is still poorly understood. Here we summarized the recent progress on the molecular mechanism of the non-host resistance, plant-pathogen interaction systems, PEN1 encoding SNARE protein mediated non-host disease resistance, and its future prospect.