Data of 11 infants (median gestational age and birth weight 30 weeks and 1520 g, respectively) with severe human rhinovirus infection (HRV) are described. Nine of 11 (82%) were preterm infants and 7 of these 9 (78%) became infected during their stay in the neonatal intensive care unit. All infants presented with respiratory distress and all needed respiratory support for a median of 6 days. Radiologic findings included perihilar streakiness, atelectasis, focal consolidation, and hyperinflation. The diagnosis of HRV infection was made by real-time polymerase chain reaction in nasopharyngeal aspirate. All infants recovered from their HRV infection. HRV can cause severe disease in preterm infants requiring respiratory support.