In this review, an attempt has been made to scrutinize mechanisms controlling disease or resistance from the perspective of biological forces and constraints affecting co-evolution of a fungal pathogen with its plant host. We reckon that plants are naturally resistant to almost all potentially pathogenic organisms. Defense mechanisms responsible for this default resistance, also termed nonhost or general resistance, are many and include both physical and chemical factors triggered rapidly in response to attempted infection. Pathogenic organisms have to contend with these mechanisms before they can succeed in colonizing a plant. It appears that two different strategies, biotrophic and necrotrophic, have evolved in fungi for this purpose. In the former, defenses are not allowed to be triggered, and in the latter these mechanisms are suppressed or nullified. Consequently, two different kinds of resistance mechanisms have evolved in plants. Against biotrophs, resistance genes function to ensure that normal plant defenses are triggered in time to keep the plant resistant to the pathogen. Against necrotrophs, resistance genes operate to negate the key pathogenic strategy of the invader. Further evolution between the host and the pathogen, and hence durability of a disease resistance gene, is governed by the importance of the fungal target of a disease resistance gene in plant pathogenesis. Key words: disease resistance, plant–fungal interaction, plant pathogenesis, gene-for-gene interaction, defense mechanisms.