Thyroid hormone (TH, T₃) is required for the normal function of most tissues, with major effects on O₂ consumption and metabolic rate. These are due to transcriptional activation of respiratory genes through the interaction of T₃-liganded TH receptors with TH response elements or the activation of intermediate factors, with the consequent higher rates of mitochondrial oxidative phosphorylation and reactive O₂ species (ROS) generation and antioxidant depletion. The genomic effects of TH are accompanied by redox upregulation of the liver expression of cytokines (tumor necrosis factor-alpha [TNF-alpha]), enzymes (manganese superoxide dismutase), and anti-apoptotic proteins (Bcl-2), via a cascade initiated by TNF-alpha produced by Kupffer cells and involving inhibitor of kappa-B phosphorylation and nuclear factor-kappa-B activation. Thus, TH calorigenesis triggers non-genomic effects leading to an expression pattern that may represent an adaptive mechanism to re-establish redox homeostasis and promote cell survival under conditions of ROS toxicity secondary to TH-induced oxidative stress. Mechanisms of expression of respiratory and redox-sensitive genes may be functionally integrated, which could be of importance to understand the complexities of TH action and the outcome of thyroid gland dysfunction.