Rice is a staple food crop and forms an important component of the diet of most Indians. A significant amount of rice production is lost due to diseases. Rice sheath blight is a very important disease of rice with estimated yield losses ranging from 6-70% depending on environmental factors such as the weather conditions. The disease is caused by the necrotrophic fungal pathogen, Rhizoctonia solani, and till now not a single source of complete disease resistance has been identified. A few QTLs for sheath blight tolerance have been identified. One of them has been used in molecular breeding but the tolerance provided has been limited. At present, the disease is mostly controlled by spraying fungicides. These fungicides tend to be detrimental to the environment and can also have adverse effects on the health of farmers/farm labourers and consumers. Therefore, controlling sheath blight disease in an eco-friendly manner remains a challenge for sustainable rice cultivation. Several research leads have been identified which if pursued further could be helpful in developing sheath blight tolerant rice varieties. These include identification of candidate susceptibility determinants in rice whose knockdown provides enhanced sheath blight tolerance in rice. A rice land race from the North-East India with enhanced tolerance to sheath blight has been identified. Introgression lines showing tolerance to sheath blight have been developed with the land race. Moreover, a novel antifungal protein has been identified from a mycophagous bacterium which can be used to develop formulations to control sheath blight disease in rice. Under a multi-institutional flagship program funded by the Department of Biotechnology, Government of India, we propose to explore these multiple leads to develop sheath blight tolerance in rice cultivars as well as novel anti-fungal formulations that are both potent and environment-friendly.