The daily oral ingestion of supplementary creatine monohydrate can substantially elevate the creatine content of human skeletal muscle. This chapter aims to summarize the current knowledge regarding the impact muscle creatine loading can have on exercise performance and rehabilitation. The major part of the elevation of muscle creatine content is already obtained after one week of supplementation, and the response can be further enhanced by a concomitant exercise or insulin stimulus. The elevated muscle creatine content moderately improves contractile performance in sports with repeated high-intensity exercise bouts. More chronic ergogenic effects of creatine are to be expected when combined with several weeks of training. A more pronounced muscle hypertrophy and a faster recovery from atrophy have been demonstrated in humans involved in resistance training. The mechanism behind this anabolic effect of creatine may relate to satellite cell proliferation, myogenic transcription factors and insulin-like growth factor-1 signalling. An additional effect of creatine supplementation, mostly when combined with training, is enhanced muscle glycogen accumulation and glucose transporter (GLUT4) expression. Thus, creatine may also be beneficial in sport competition and training characterized by daily glycogen depletion, as well as provide therapeutic value in the insulin-resistant state.