The high-energy demand during high-intensity exercise (HIE) necessitates that anaerobic processes cover an extensive part of the adenosine triphosphate (ATP) requirement. Anaerobic energy release results in depletion of phosphocreatine (PCr) and accumulation of lactic acid, which set an upper limit of anaerobic ATP production and thus HIE performance. This report focuses on the effects of training and ergogenic supplements on muscle energetics and HIE performance. Anaerobic capacity (i.e. the amount of ATP that can be produced) is determined by the muscle content of PCr, the buffer capacity and the volume of the contracting muscle mass. HIE training can increase buffer capacity and the contracting muscle mass but has no effect on the concentration of PCr. Dietary supplementation with creatine (Cr), bicarbonate, or beta-alanine has a documented ergogenic effect. Dietary supplementation with Cr increases muscle Cr and PCr and enhances performance, especially during repeated short periods of HIE. The ergogenic effect of Cr is related to an increase in temporal and spatial buffering of ATP and to increased muscle buffer capacity. Bicarbonate loading increases extracellular buffering and can improve performance during HIE by facilitating lactic acid removal from the contracting muscle. Supplementation with beta-alanine increases the content of muscle carnosine, which is an endogenous intracellular buffer. It is clear that performance during HIE can be improved by interventions that increase the capacity of anaerobic ATP production, suggesting that energetic constraints set a limit for performance during HIE.