Host-selective toxins, a group of structurally complex and chemically diverse metabolites produced by plant pathogenic strains of certain fungal species, function as essential determinants of pathogenicity or virulence. Investigations into the molecular and biochemical responses to these disease determinants reveal responses typically associated with host defense and incompatibility induced by avirulence determinants. The characteristic responses that unify these disparate disease phenotypes are numerous, yet the evidence implicating a causal relationship of these responses, whether induced by host-selective toxins or avirulence factors, in determining the consequences of the host-pathogen interaction is equivocal. This review summarizes some examples of the action of host-selective toxins to illustrate the similarity in responses with those to avirulence determinants.