Efforts to improve medication safety in hospital settings often target nurses, such as utilizing barcode medication administration or limiting interruptions during nurses' medication administration tasks. Nurses can also support medication safety by speaking up about medication orders that appear to be incorrect. In this interview study, neonatal intensive care unit nurses were asked to describe scenarios in which they did and did not question medication administration. Investigators found that nurses spoke up about medication administration because of concern for patients and when they felt confident in their medication knowledge. Nurses' work environment could bolster or hinder questioning of medication administration. Interventions to support a positive safety culture and to enhance nurses' medication knowledge could reinforce safe medication administration.