Background:- Leptin is a pleiotropic hormone produced mainly by the adipose tissue. Its most well-known effect is to regulate food intake and energy metabolism within the hypothalamus. More recently, several peripheral and extra-hypothalamic effects have been described, expanding leptin's actions far beyond energy balance. Aims:- To review the extra-hypothalamic effects of leptin and their possible clinical implications. Methods:- We did a PubMed search using the terms "leptin" AND "brain" AND "neuron" AND "glial", and selected the most relevant articles. Results:- In extra-hypothalamic sites, leptin has remarkable effects on neurogenesis, axon growth, synaptogenesis, denditric morphology, development of oligodendroglial cells, neuron excitability, neuroprotection and regulation of beta-amyloid levels. Those effects have been shown to improve cognition and mood in animal models of depression and anxiety. In lean humans, leptin levels have been negatively correlated with the development of Alzheimer's disease. Conclusions:- Leptin has extra-hypothalamic effects that may protect the brain against the development of mood and neurodegenerative disorders, such as Alzheimer's disease. Better understanding of those effects may lead to the development of potential leptin-based therapies against such conditions.