Nurse leaders play a critical role in patient safety. They are essential in building a culture of safety and engineering resilience into workflows and patient care processes enabling healthcare organizations to progress toward high reliability. In part 1 of this 2-part series, the authors discuss the critical nature of a safety culture: why trust and respect lead to teamwork and collaboration in preventing serious safety events. Part 2 will introduce the emerging healthcare concept of high reliability, described through examples of health systems that have successfully adapted models from other industries. Use of technology and other advancements provides a context for advancing patient safety. Aligning culture and engineering technology for safety, when coupled with effective leadership, can provide a long-term approach for safe and effective care.