Idiopathic arterial calcification of infancy is a rare condition characterized by extensive calcification and stenosis of the large and medium sized arteries. Approximately 100 cases have been reported worldwide, with the majority of patients being Caucasians. The disease most commonly occurs in infants less than six months of age. Severe systemic hypertension, cardiomyopathy, and congestive heart failure are frequent complications. Associated anomalies are rare, and include non-specified cardiac anomalies, hydronephrosis, polycystic kidneys, trisomy 17 and 18. Pathologically, the condition is characterized by deposition of calcium along the internal elastic membrane of arteries, accompanied by fibrous thickening of the intima, which causes luminal narrowing. The arterial lesions are widespread, but the resultant luminal narrowing invariably leads to coronary arterial occlusion and myocardial ischemia. The etiology is not completely understood. There is evidence of familial clusters. As an autosomal recessive inheritance is suggested, consanguinity increases the risk of developing the disease. Recently, the disease has been found with mutations that inactivated ecto-nucleotide pyrophosphatase/phosphodiesterase 1. Clinical diagnosis is feasible with radiologic studies, including angiography, or computerized tomographic scans of arteries of the head, neck, and extremities. Antenatal diagnosis has been reported, with findings of arterial calcifications, hydrops, abnormal cardiac contractility, and hyperechoic kidneys. The diagnosis is essential for genetic counseling, and for screening of siblings at risk for developing the disease. Differential diagnosis includes endocardial fibroelastosis, myocardititis, storage disorders, infarction, anomalous insertion of the coronary arteries, cardiac anomalies, metastatic calcification due to renal disease, hypervitaminosis D, and infections. The disease should also be added to the list of differential diagnoses for non-immune fetal hydrops. There is no specific treatment, and prognosis is poor. Most infants die from myocardial infarction within the first year of life, with the greatest number of deaths occurring within the first six months.