Adiponectin is an important adipocyte-derived hormone that regulates metabolism of lipids and glucose, and its receptors (AdipoR1, AdipoR2, T-cadherin) appear to exert actions in peripheral tissues by activating the AMP-activated protein kinase, p38 mitogen-activated protein kinase, peroxisome proliferator activated receptor α and nuclear factor-kappa B. Adiponectin has been shown to exert a wide range of biological functions that could elicit different effects, depending on the target organ and the biological mileu. There is substantial evidence to suggest that adiponectin receptors are expressed widely in the brain. Their expression has been detected in regions of the mouse hypothalamus, brainstem, cortical neurons and endothelial cells, as well as in whole brain and pituitary extracts. While there is now considerable evidence for the presence of adiponectin and its receptors in the brain, their precise roles in brain diseases still remain unclear. Only a few research studies have looked at this facet of adiponectins in brain disorders. This brief review will describe the evidence for important functions by adiponectin, its structure and known actions, evidence for expression of AdipoRs in the brain, their involvement in brain disorders, and the therapeutic potential of agents that could modify AdipoR signalling.