Melatonin is well known as a neuroendocrine hormone that promotes sleep. However, the many other attributes of melatonin are less apparent and not as widely appreciated. The purpose of this review is to summarize the qualities of melatonin relating to immune function. The relevance of melatonin in partially or wholly restoring optimal function, in a series of disorders related to immune dysfunction, is addressed in this report. This includes the potential relief of both autoimmune diseases and many other ailments involving abnormal immune responses, including the overall diminished effectiveness of body defenses occurring with aging. Disease states affecting a wide range of organ systems have been reported as benefitting from melatonin administration and are discussed here. A separate section addresses the potential role of melatonin in the mitigation of age-related neurological diseases, in view of the increasing importance of this area. The likely mechanistic basis of the properties by which melatonin may confer protection by its acting on immune function is also described.