INTRODUCTION: Several recent developments in melatonin research deserve attention and divulgation. The role of melatonin in the brain has been extended to its synthesis in the cerebellum as a response to inflammation, findings that exceed the earlier demonstration of aralkylamine Nacetyltransferase expression. The release of melatonin via the pineal recess into the third ventricle appears to be more important than previously believed and has been discussed as a strong direct signal to the suprachiasmatic nucleus. The mitochondrial role of melatonin has been substantially extended by the demonstration of the melatonin receptor MT1 in this organelle and evidence for melatonin synthesis in mammalian mitochondria, in addition to the previously shown uptake into these organelles. Contrary to rats and mice, melatonin can act in a prodiabetic way, especially under conditions of MT2 overexpression, an effect that leads to reduced insulin secretion. These findings are discussed in the context of brain insulin resistance as an early change in low-grade neuroinflammation, however, with emphasis to the distinction between reduced insulin and insulin resistance. Various new data underline the stimulation of sirtuins 1 and 3 by melatonin in the context of aging and of inflammation. Data support a nexus between sirtuins, circadian oscillators and melatonin, and hints for the transduction of melatonin effects by sirtuin 1. Further transduction mechanisms concern the upregulation of microRNAs as well as their transmission via exosomes. CONCLUSION: The recent findings on melatonin have also to be seen in their consequences to the use of synthetic melatonergic agonists.