The overtraining syndrome is characterized by an excessive training that results in several adverse effects the main of which being the decay in performance. Its incidence among elite athletes has been experiencing a significant increase lately, which prompted a rush of interest in the search for efficient measures to prevent and treat this condition. It is necessary, however, to clarify possible mechanisms involved in the development of overtraining. Several hypothesis are being proposed, such as a greater activation of both the autonomic nervous system and the hypothalamic-pituitary-adrenal axis, and suppression of the hypothalamic-pituitary-gonadal axis. On the contrary, some studies suggest that the modulation of such systems is but a consequence of the overtraining syndrome and not its cause. Thus, recent hypothesis related to cytokine release, to central fatigue, to depletion of muscle and liver glycogen, and to a reduction in glutamine availability during physical activity are being raised.