Apart from being the main energy reserves of the human body, triacylglycerols take part in metabolic processes that determine the rate of fatty acid oxidation, the plasma levels of free fatty acids, the biosynthesis of other lipid molecules and the metabolic fate of lipoproteins. Allosteric, hormonal, nutritional and transcriptional signals activate short-term and long-term regulatory mechanisms that assure the storage of triacylglycerols (TAGs) under states of excess energy and their mobilization under conditions of metabolic stress. New enzymes and novel regulatory mechanisms, involved in triacylglycerol metabolism, have been recently discovered and new details on the fine tuning of their metabolic reactions are coming to light. This knowledge will help us understand the biochemical basis of several diseases for the pathogenesis of which triacylglycerols play a role.