Leptin and ghrelin are two hormones associated with multiple physiological functions, especially energy balance. Leptin is an adipocyte-secreted hormone discovered in 1950 and ghrelin which was found in 1999, is a peptide hormone produced and secreted in the stomach. A number of previous studies showed that these hormones could be associated with different types of mood disorders. The results of previous studies, nevertheless, are confounded by diverse sample selection and different methodologies. A search for related articles in the PubMed database was attempted. The search covered studies, reports, reviews and editorials published in the last ten years. Older references served as auxiliary sources for comparison purposes. However, due to the different results of the studies, there is a need for more investigation in order to establish the exact biochemical mechanisms that are responsible for these diseases and ghrelin's and leptin's effects on mood. Core tip: Mood disorders are affecting a major amount of the world population. Considering the multiple factors that are contributing in the development of mood disorders, this review emphasizes on the role of leptin and ghrelin hormones. These two hormones have a key role in energy balance but they also have an effect on other physiological functions too, therefore we emphasize on the recent findings which raise a potential link between the hormones and the disorders of mood.