Nephrocalcinosis occurs in as many as 40% of preterm neonates. Many causes and contributors predispose neonates to develop nephrocalcinosis, including metabolic, genetic, and iatrogenic factors. Because nephrocalcinosis can be a manifestation of an underlying genetic disorder, neonates with nephrocalcinosis must undergo an evaluation to identify and address contributors, to prevent further renal calcium deposition that can potentially lead to renal dysfunction. In this article, we review the epidemiology, pathogenesis, diagnosis, and evaluation of nephrocalcinosis in neonates. We also summarize the natural history of nephrocalcinosis of prematurity as well as the management of this condition.