Intensive care delirium is a well-recognized complication in critically ill patients. Delirium is an independent risk factor for death in the intensive care unit (ICU), leading to oversedation, increased duration of mechanical ventilation, and increased length of stay. Although there has not been a direct causal relationship shown between sleep deprivation and delirium, many studies have demonstrated that critically ill patients have an altered sleep pattern, abnormal levels of melatonin, and loss of circadian rhythms. Melatonin has a major role in control of circadian rhythm and sleep regulation and other effects on the immune system, neuroprotection, and oxidant/anti-oxidant activity. There has been interest in the use of exogenous melatonin as a measure to improve sleep. However, there are only a few studies of melatonin in ICU patients and these use heterogeneous methodologies. Therefore, it is not possible at this stage to make any clear recommendations regarding the clinical use of melatonin in this setting. There is a need for well-designed randomized controlled trials examining the role of melatonin in ICU.