The branched-chain amino acids (BCAAs), namely, valine, leucine, and isoleucine, are indispensable amino acids required for body protein synthesis. Unlike other amino acids, the BCAAs are primarily catabolised in the extrahepatic tissues. The BCAAs play role in regulation of protein synthesis and turnover as well as maintenance of the body glutamate-glutamine level. In strenuous and traumatic conditions, the BCAAs are oxidized which limits their availability in tissues. Such condition affects the body glutamate-glutamine pool and protein synthesis mechanisms. Thus BCCA supplementation is emerging as a nutritional strategy for treating many diseases. Many studies have found that BCAA administration is able to improve the health status of the patients suffering from different diseases even though there are conditions where they do not exert any effect. There are also some reports where elevated BCAAs have been shown to be associated with the pathogenesis of diseases. In this review, we have discussed the implication of BCAA supplementation in different pathological conditions and their relevant outcomes.