Interactions between plants and microbes result in plant disease and symbiosis. The former causes considerable economic damage in modern agriculture, while the latter has produced great beneficial effects to our agriculture system. Comparison of the two interactions has revealed that a common panel of signaling pathways might participate in the establishment of the equilibrium between plant and microbes or its break-up. Plants appear to detect both pathogenic and symbiotic microbes by a similar set of genes. All symbiotic microbes seem to produce effectors to overcome plant basal defenses and it is speculated that symbiotic effectors have functions similar to pathogenic ones. Signaling molecules, salicylic acid (SA), jasmonic acid (JA) and ethylene (ET), are involved in both plant defense and symbiosis. Switching off signals contributing to deterioration of disease symptom would establish a new equilibrium between plant and pathogenic microbes. This would facilitate the development of strategies for durable disease resistance. Interactions between plants and microbes result in plant disease and symbiosis. The former causes considerable economic damage in modern agriculture, while the latter has produced great beneficial effects to our agriculture system. Comparison of the two interactions has revealed that a common panel of signaling pathways might participate in the establishment of the equilibrium between plant and microbes or its break-up. Plants appear to detect both pathogenic and symbiotic microbes by a similar set of genes. All symbiotic microbes seem to produce effectors to overcome plant basal defenses and it is speculated that Signaling molecules, salicylic acid (SA), jasmonic acid (JA) and ethylene (ET), are involved in both plant defense and symbiosis. Switching off signals contributing to deterioration of disease symptom would establish a new equilibrium between plant and pathogenic microbes. This would facilitate the development of strategies for durable disease resistance.