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Background: Oxidative stress (OS) arises when the balance between the production of oxidants and their removal is disturbed; OS is associated with a wide variety of health disorders. Finding strategies that efficiently reduce OS is an active area of research. Objective: This review summarizes the chemical insights concerning the antioxidant capacity (AOC) of melatonin and related compounds. Method: We consider not only naturally-occurring but also synthetic derivatives. Different chemical routes that may be involved in their AOC are analyzed and some trends in activity are provided. Conclusion: Based on the data gathered so far it can be stated that melatonin and related compounds constitute a chemical family with remarkable protective effects against OS. Their action includes both primary and secondary AOC, and -collectively- they can be considered as multifunctional protectors against OS. Current challenges and future perspectives in this area of research are discussed.