<p>Chikungunya is a re-emerging neglected tropical disease that has recently become aglobal health concern due to its increasing burden and substantial geographicalexpansions. It is caused by the Chikungunya virus (CHIKV, an alphavirus), whichbelongs to the family Togaviridae and is transmitted by the Aedes mosquito. TheChikungunya infection is usually self-limiting during the acute phase, but incapacitatingarthralgia is the major cause of morbidity. At present, no specific antiviral is availablefor treatment, and current guidelines generally aim to reduce symptoms rather thantarget the virus directly. Recently, two vaccine approved for high-risk population andtravelers; however, these vaccines are not incorporated into routine immunizationprogrammes. There is an urgent need to develop a direct acting antiviral againstCHIKV. With respect to CHIKV, many proteins (structural or non-structural) can bepotential targets against which compounds can be developed or identified and hence,considering the pivotal role of non-structural proteins in viral replication, interaction withhost cells, and virus propagation. Therefore, non-structural proteins are potentialtargets for antiviral intervention. The present review aims to unravel the structure andfunctions roles of Chikungunya non-structural proteins to understand domain-specificpathogenesis and disease progression.</p>