Disease is one of the devastating obstacles in the stable crop production. Numerous agronomical and chemical controls have been developed to overcome this problem, but the former is not sufficient for the maintaining the disease under the economic threshold level and the latter is not free from the environmental regulation. One of the most ideal solutions is resistance breeding. Resistance breeding has been majorly dependent on the resistance (R) genes conferring race-specific vertical resistance effective for limited populations within the pathogen species harboring avirulence (Avr) genes encoding effectors exactly matching with R gene products. In spite of its outstanding efficiency, improper management of above cultivars frequently resulted in the resistance break down due to the appearance and domination of the new races in the field. During the last two decades, mechanisms of disease resistance have been characterized and analyzed in the respect of genetics, biochemistry, molecular biology, cell biology, and evolution. Especially, a growing body of investigations has been focused on the resistance effective for multiple races or even more species of pathogen’s infections and also durable and long-lasting. In this manuscript, we will introduce the investigations searching for durable and broad-spectrum resistance and the considerations for their applications in the crop production will be presented.