Muscle mass is a key factor in the performance and health of athletes. Skeletal muscle mass is determined by the balance between muscle protein synthesis (MPS) and muscle protein breakdown (MPB). One of the goals of strength athletes is to have more muscle mass through exercise, nutritional, and supplementation strategies. From a supplementation perspective, creatine supplementation, especially when combined with resistance training, is recognized as a strategy for increasing lean tissue mass and muscle strength. The mechanisms of action of creatine in skeletal muscle include increased energy availability, IGF-1 signaling, activation of the mTOR pathway, increased intracellular water, activation of satellite cells, reduced muscle damage, and improved recovery, which are discussed in this review. This article provides a comprehensive review of the current literature on creatine supplementation and its effects on MPS in athletes. We review the mechanisms through which creatine exerts its effects, its implications for different types of exercise training, and considerations for optimal dosing protocols.