Melatonin is a multifunctional signalling molecule that is secreted by the mammalian pineal gland, and also found in a number of organisms including plants and bacteria. Research has continued to uncover an ever-increasing number of processes in which melatonin is known to play crucial roles in mammals. Amongst these functions is its contribution to cell multiplication, differentiation and survival in the brain. Experimental studies show that melatonin can achieve these functions by influencing transcription factors which control neuronal and glial gene expression. Since neuronal survival and differentiation are processes that are important determinants of the pathogenesis, course and outcome of neurodegenerative disorders; the known and potential influences of melatonin on neuronal and glial transcription factors are worthy of constant examination. In this review, relevant scientific literature on the role of melatonin in preventing or altering the course and outcome of neurodegenerative disorders, by focusing on melatonin's influence on transcription factors is examined. A number of transcription factors whose functions can be influenced by melatonin in neurodegenerative disease models have also been highlighted. Finally, the therapeutic implications of melatonin's influences have also been discussed and the potential limitations to its applications have been highlighted.