Thyroid hormones act as pleiotropic factors in many tissues during development, by regulating genes involved in differentiation. The adipose tissue, a target of thyroid hormones, is the main place for energy storage and acts as a regulator of energy balance, sending signals to keep metabolic control. Adipogenesis is a complex process that involves proliferation of preadipocytes and its differentiation into mature adipocytes. This process is regulated by several transcription factors (CCAAT/enhancer-binding proteins [C/EBPs], peroxisome proliferator-activated receptors [PPARs]) that act coordinately, activating adipocyte-specific genes that will provide the adipocytic phenotype. Thyroid hormones regulate many of those genes, markers of differentiation of adipocytes, those involved in lipogenesis, lipolysis, and thermogenesis in the brown adipose tissue (BAT). Triiodothyronine (T3) actions are achieved either directly through specific thyroid response elements (TREs), by regulating other key genes as PPARs, or through specific isoforms of the nuclear T3 receptors. The availability of T3 is regulated through the deiodinases D3, D2, and D1. D3 is activated by serum and mitogens during proliferation of preadipocytes, while D2 is linked to the differentiation program of adipocytes, through the C/EBPs that govern its functionality, providing the T3 required for thermogenesis and lipogenesis. The relationship between white adipose tissue (WAT) and BAT and the possible reactivation of WAT by activation of uncoupling protein-1 (UCP1) is discussed.