Five years after the landmark report of the Institute of Medicine To Err Is Human (Kohn, Corrigan, and Donaldson 2000), many are asking, "Is U.S. healthcare safer?" A number of articles addressing this question have been written, interviews with nationally recognized patient safety leaders have been published, and governing boards of many healthcare organizations are examining reports of care provided by their institutions. Robert M. Wachter, writing in the November 2004 issue of Health Affairs, concludes that, "At this point, I would give our efforts an overall grade of C+, with striking areas of progress tempered by clear opportunities for improvement." We describe in this article the pursuit of a culture of safety at William Beaumont Hospital in Royal Oak, Michigan. Our experience has offered us the opportunity to ponder a number of key questions: How does leadership guide an organization toward a culture of safety? Does culture truly drive behavior, or is it really the reverse? How can a culture of safety be measured or observed? What levels of resources and commitment are required for success? Is safety all about systems and processes, or are core values also involved? What role does the patient play in ensuring safe care? We attempt to offer guidance, and share lessons learned, for each of these important questions.