The adaptation of species to the environment in which they live is accomplished by so-called “clocks” that allow the biological, physiological, metabolic and behavioral system to correct any development during the day. The alteration of those ‘clocks’ (circadian rhythms) shows a strong relationship with organic disorders such as neurodegenerative diseases. Many studies show that oxidative stress combined with pro-inflammatory mechanisms, play a key role in the development of neurodegenerative diseases and psychiatric disorders. Oxidative stress is fought by many antioxidant molecules. Melatonin, a hallmark of circadian rhythm functionality, is a natural antioxidant with a circadian secretion pattern. The mechanisms involved in the antioxidant properties of melatonin are complex but its depletion or lack unequivocally leads to cell damage. This process is also linked to the disruption of the circadian rhythm. A disrupted circadian rhythm followed by oxidative stress and inflammatory processes could be the pathophysiological basis for several disorders of the central nervous system. In the current review we will analyze those interactions. We will focus on the relationship between melatonin and its light/dark rhythms of secretion and how the antioxidant properties of melatonin opens a new therapeutic hope against central nervous system disorders.