The lipids of metabolic significance in the mammalian organisms include triacylglycerols, phospholipids and steroids, together with products of their metabolism such as long-chain fatty acids, glycerol and ketone bodies. The fatty acids which are present in the triacylglycerols in the reduced form are the most abundant source of energy and provide energy twice as much as carbohydrates and proteins. Fatty acids represent an important source of energy in periods of catabolic stress related to increased muscular activity, fasting or febrile illness, where as much as 80% of the energy for the heart, skeletal muscles and liver could be derived from them. The prime pathway for the degradation of fatty acids is mitochondrial fatty acid β-oxidation (FAO). The relationship of fat oxidation with the utilization of carbohydrate as a source of energy is complex and depends upon tissue, nutritional state, exercise, development and a variety of other influences such as infection and other pathological states. Inherited defects for most of the FAO enzymes have been identified and characterized in early infancy as acute life-threatening episodes of hypoketotic, hypoglycemic coma induced by fasting or febrile illness. Therefore, this review briefly highlights mitochondrial β-oxidation of fatty acids and associated disorders with clinical manifestations.