Probiotic use has increased in preterm infants and may reduce the risk of necrotizing enterocolitis. Probiotic-associated infection is a concern for infants receiving probiotic supplementation in the neonatal intensive care unit, as highlighted by a recent case and subsequent action by the United States Food and Drug Administration. Based on reports to date, invasive infection is an infrequent but known risk of probiotic supplementation. In this article, we discuss the epidemiology and pathophysiology of invasive infection in preterm infants, review the benefits and risks of probiotic as regulations and available products continue to evolve.