The gene-for-gene relationship of host–pathogen interaction explained by H. H. Flor in mid of the 20th century set a milestone in understanding the biochemical and genetic basis of plant diseases and several components involved in plant–pathogen interactions. It highlighted the importance of accomplishing differential sets and understanding the pathogen population structure, it further led to theidentification and cloning of several resistance (R) genes in plants. These R genes have been deployed and altered for fighting against diseases in a large number of crops using various conventional approaches and biotechnological tools. Identification of R genes and their corresponding Avr genes in many cases played a significant role in understanding of R-Avr gene interactions. Rapid cloning of R genes and editing of susceptible R genes are the other avenues that have broadened the horizon of utilizing R genes in crop improvement programmes. Further, combining R genes with quantitative disease resistance genes has paved the way to develop durable resistance in cultivars. Therecent advances in genetics, genomics, bioinformatics and other OMICS tools are now providing greater prospects for deeper understanding of host–pathogen interaction.