Mitochondrial fatty acid β-oxidation disorders are a heterogeneous group of congenital errors of metabolism that are inherited in an autosomal recessive way. Fatty acids undergo mitochondrial β-oxidation, the catabolic process by which fatty acid molecules are broken down when fat is needed as an energy source, during periods of decreased energy intake or increased energy demands. So far, eight different disorders have been described. These disorders are characterized by different age of onset, severity and a wide variety of clinical manifestations, mostly related to the damage of high metabolic demanding organs. There are three variable clinical forms of disease in all ages. The neonatal phenotype is the most severe, life-threatening presentation of these disorders. Patients usually present with severe hepatopathy, cardiomyopathy and skeletal myopathy, whereas some patients may suffer encephalopathy. The infantile phenotype presents in infancy, early childhood or pre-school age with intermittent episodes of lethargy, vomiting, hypoglycemia, liver dysfunction, rhabdomyolysis and cardiomyopathy, usually associated with intercurrent illnesses. Some patients can be without symptoms for years, although at risk of severe metabolic decompensation and organ damage during illness, fasting and other stressful conditions. The myopathic type presents at a later age, with episodes of muscle weakness, myalgias, rhabdomyolysis, and risk of renal damage. Accumulation of the specific acylcarnitine species in blood and organic acids in urine is characteristic of these disorders. Hypoketotic hypoglycemia often occurs during the crisis. Mostly, elevated levels of ammonia, creatine kinase and aminotransferases are present. To confirm the diagnosis, genetic testing or measurement of enzyme activity should be done. Since early diagnosis and early initiation of treatment are improving outcomes, fatty-acid-oxidation disorders are part of a newborn screening in many countries.