Despite an increased focus on the quality and safety of care, the United States health care system does not reliably deliver safe, high-quality care for all women and infants. In many cases, a gap still exists between best evidence and routine practice and pregnant women and neonates continue to experience preventable harm. Effective change strategies targeting individuals, groups or teams, organizations, and the larger system or environment have been used in the setting of perinatal care to improve quality and safety. In addition, strategies focused on aligning change efforts across multiple levels are increasingly being used to more effectively change practice in the context of the complex health care system. This review examines some of the single-level and multilevel approaches to changing practice that have been used in perinatal safety and quality improvement. Although progress has been slow, improvements in quality and safety measurement, widespread commitment to implementing effective practice change interventions, and advances in perinatal improvement and implementation research will help ensure that the dramatic improvements in perinatal quality and safety that have been anticipated will truly be realized.