A large number of studies have been published on creatine supplementation over the last decade. Many studies show that creatine supplementation in conjunction with resistance training augments gains in muscle strength and size. The underlying physiological mechanism(s) to explain this ergogenic effect remain unclear. Increases in muscle fiber hypertrophy and myosin heavy chain expression have been observed with creatine supplementation. Creatine supplementation increases acute weightlifting performance and training volume, which may allow for greater overload and adaptations to training. Creatine supplementation may also induce a cellular swelling in muscle cells, which in turn may affect carbohydrate and protein metabolism. Several studies point to the conclusion that elevated intramuscular creatine can enhance glycogen levels but an effect on protein synthesis/degradation has not been consistently detected. As expected there is a distribution of responses to creatine supplementation that can be largely explained by the degree of creatine uptake into muscle. Thus, there is wide interest in methods to maximize muscle creatine levels. A carbohydrate or carbohydrate/protein-induced insulin response appears to benefit creatine uptake. In summary, the predominance of research indicates that creatine supplementation represents a safe, effective, and legal method to enhance muscle size and strength responses to resistance training.