Despite considerable investment and advances in patient safety, there are still hundreds of thousands of patients being harmed by medical error each year. A different way of thinking is required to ‘move the needle’ on patient safety. Human factors approaches underpin current patient safety and quality improvement science, offering an integrated, evidenced, and coherent approach to patient safety, quality improvement, and clinical excellence. Human factors rests on a systems approach — one must examine the human, interactions, and inter-dependencies within a larger system in order to optimize performance. The system-wide adoption of these concepts offers a unique opportunity to support cultural change and empower clinicians to put patient safety and clinical excellence at the center of their work. Human factors and systems safety focus on re-designing work as opposed to re-designing the human who does the work. Incorporating a human factors and systems safety approach allows for the development and integration of knowledge, skills and attitudes that facilitate successful performance at the front lines of care. This approach will help identify safe, sustainable and resilient solutions.