Citrulline is a nonessential amino acid with properties that were unknown or largely ignored until the last decade when it began to arouse the interest of scientists due to its key role in the regulation of nitrogen homeostasis. It has since emerged as a key activator of muscle protein synthesis in catabolic situations, via activation of mTOR pathway (mammalian Target of Rapamycin). The activation of muscle protein synthesis is associated with an increase in muscle protein content and muscle mass, leading to better motricity. Interestingly, these effects have recently been partially confirmed in healthy animals. Importantly, the benefit of citrulline for muscle metabolism has also been observed in humans, but the benefit for performance is mixed. Despite the recent surge in data on the effects of citrulline on muscle, further explorations are still needed in order to gain a complete overview of the role of citrulline in muscle metabolism and the mechanisms involved.