Tumor necrosis factor-alpha (TNF alpha) is a multifunctional cytokine which exerts a myriad of biological actions in different tissues and species. Many of these actions can perturb the normal regulation of energy metabolism. In adipose tissue, in particular, TNF alpha has been demonstrated to regulate or interfere with adipocyte metabolism at numerous sites including transcriptional regulation, glucose and fatty acid metabolism and hormone receptor signaling. The implications of these perturbations in disease states and the current understanding of the molecular mechanisms utilised by TNF alpha are discussed herein.