Since 1999, patient safety has become a national priority. That year, the Institute of Medicine of the National Academy of Sciences issued two landmark reports that set a challenge to all levels of healthcare professionals to improve the safety and quality of care for all patients and families. Medically fragile NICU patients are at a great risk for medical errors that lead to adverse events due to the fast-paced and complex environment. Due to the emphasis on creating a culture of safety and transparency, neonatal units across the country are making progress to provide consist, safe, and evidence-based care. The goal remains to identify, report, and learn from near misses, precursor events, and serious safety issues. This will permit healthcare systems to evolve into high-reliability organizations (HROs) with patient safety being at the forefront.