Although various government and regulatory organisations have identified practices that may enhance patient safety, there is little empirical or theoretical research to inform the decisions of healthcare leaders seeking to create patient safety programmes within their hospitals and clinics. In order to understand the challenges facing hospital and health system executives, we describe the experience of the Executive Session on Patient Safety. The executives identified five major problems in leading patient safety: 1) how should executives structure their organisations to deliver safe care? 2) how should executives monitor and measure their organisation's safety performance? 3) how should executives spread and sustain patient safety innovation? 4) how should executives manage the relationship with the external environment? and 5) how should executives manage their own behaviour in order to lead for safety? The organisational infrastructure needed for safer care is being developed by practitioners out in the field as a matter of necessity. Strengthening the scientific basis for organisational leadership in patient safety is a vital but neglected area of study.