Melatonin is an indolamine synthesized and secreted by the pineal gland along with other extrapineal sources including immune system cells, the brain, skin and the gastrointestinal tract. Growing interest in this compound as a potential therapeutic agent in several diseases stems from its pleiotropic effects. Thus, melatonin plays a key role in various physiological activities that include regulation of circadian rhythms, immune responses, the oxidative process, apoptosis or mitochondrial homeostasis. Most of these processes are altered during inflammatory pathologies, among which neurodegenerative and bowel diseases stand out. Therapeutic assays with melatonin indicate that it has a beneficial therapeutic value in the treatment of several inflammatory diseases, such as Alzheimer, Amiotrophic Lateral, Multiple Sclerosis and Huntigton´s disease as well as ulcerative colitis. However, contradictory effects have been demonstrated in Parkinson´s and Chron´s diseases, which, in some cases, the reported effects were beneficial while in others the pathology was exacerbated. These various results may be related to several factors. In the first place, it should be taken into account that at the beginning of the inflammation phase there is a production of reactive oxygen species (ROS) that should not be blocked by exclusively antioxidant molecules, since, on the one hand, it would be interfering with the action of neutrophils and macrophages and, on the other, with the apoptotic signals activated by ROS. It is also important to keep in mind that the end result of an anti-inflammatory molecule will depend on the degree of inflammation or whether or not it has been resolved and has therefore become chronic. In this review we present the use of melatonin in the control of inflammation underlying the above mentioned diseases. These actions are mediated through their receptors but also with their direct antioxidant action and melatonin's ability to break the vicious cycle of ROSinflammation. This review is aimed at evaluating the effect of melatonin on activity of the inflammatory process and at its immunomodulator effects.