The aim of this review is to provide the reader with a general overview on the rationale for the use of melatonin by military personnel. This is a technique that is being increasingly employed to manage growing psycho-physical loads. In this context, melatonin, a pleotropic and regulatory molecule, has a potential preventive and therapeutic role in maintaining the operational efficiency of military personnel. In battlefield conditions in particular, the time to treatment after an injury is often a major issue since the injured may not have immediate access to medical care. Any drug that would help to stabilize a wounded individual, especially if it can be immediately administered (e.g., per os) and has a very high safety profile over a large range of doses (as melatonin does) would be an important asset to reduce morbidity and mortality. Melatonin may also play a role in the oscillatory synchronization of the neuro–cardio–respiratory systems and, through its epigenetic action, poses the possibility of restoring the main oscillatory waves of the cardiovascular system, such as the Mayer wave and RSA (respiratory sinus arrhythmia), which, in physiological conditions, result in the oscillation of the heartbeat in synchrony with the breath. In the future, this could be a very promising field of investigation.