Since its discovery in 1995 adiponectin has garnered considerable interest from the academic, clinical and biotech communities due to its proposed salutary anti-inflammatory, anti-diabetic, anti-atherogenic and cardioprotective properties. As a result our appreciation of adiponectin’s structure and the importance of post-translational modifications (PTMs) in adiponectin production are now relatively advanced. So too, following the identification of a variety of adiponectin receptors, binding proteins and downstream signalling networks, is our understanding of adiponectin’s intracellular signalling pathways that are implicated in mediating adiponectin’s pleiotropic effects. Adiponectin’s ability to moderate inflammation, which is recognised as a key protagonist in many modern diseases, may be the key to many of its beneficial effects. Recent insights indicate that adiponectin modulates cellular inflammation by affecting sphingolipid metabolism, with the adiponectin receptors displaying intrinsic ceramidase activity. In the current review we will summarise the molecular details of adiponectin, discuss key players and recent insights into adiponectin signalling and consider the physiologic role(s) of adiponectin. We will also review studies into the effects of diet or exercise on circulating adiponectin levels focusing largely on reports from human trials.