Resistance of an entire plant species to all isolates of a microbial species is referred to as non-host or species resistance. An interplay of both constitutive barriers and inducible reactions comprises the basis for this most durable form of plant disease resistance. Activation of inducible plant defence responses is probably brought about by the recognition of invariant pathogen-associated molecular patterns (PAMP) that are characteristic of whole classes of microbial organisms. PAMP perception systems and PAMP-induced signalling cascades partially resemble those known to mediate activation of innate immune responses in animals, suggesting an evolutionarily ancient molecular concept of non-self recognition and immunity in eukaryotes. Genetic dissection has recently provided clues for SNARE-complex-mediated exocytosis and directed vesicle trafficking in executing plant non-host resistance. Recent functional analysis of bacterial effector proteins indicates that establishment of infection in susceptible plants is associated with suppression of plant species resistance.