Inborn errors of metabolism (IEM) comprise a group of disorders in which a single gene defekt causes a clinically significant block in a metabolic pathway resulting either in accumulation of substrate behind the block or deficiency of the product. IEMs are all genetically transmitted in an autosomal recessive or X-linked recessive style. The major categories are: organic acidemias, fatty acid oxidation defects, lactic acidoses, aminoacidopathies, urea cycle defects, disorders of carbohydrate metabolism, lysosomal storage disorders and paroxisomal disorders. The number of known metabolic disorders is probably as large as the number of presenting symptoms that may indicate metabolic disturbances. The topic of inborn errors of metabolism is challenging for most physicians. Detailed knowledge of biochemical pathways is not necessary to treat patients during the initial evaluation. The extensive use of tandem mass spectrometry is helping to identify more inborn errors of metabolism. Primary care physicians often are the first to be contacted by state and reference laboratories when neonatal screening detects the possibility of an inborn error of metabolism. Physicians must take immediate steps to evaluate the infant and should be able pursue additional diagnostic testing and access a regional subspecialty center. Metabolic emergencies like hypoglycemia, hyperammonemia, metabolic acidosis, and possible metabolic crises in infants and children must be treated urgently, even if the specific underlying metabolic disorder is not yet known. The early and specific diagnosis of inborn errors of metabolism and prompt initiation of appropriate therapy are still the best determinants of outcome for these patients.