Healthcare worldwide is faced with a crisis of patient safety: Notwithstanding occasional successes in relation to specific harms, safety as a system characteristic has remained elusive. We propose that one neglected reason why the safety problem has proved so stubborn is that healthcare suffers from a pathology known in the public administration literature as the problem of many hands. It is a problem that arises in contexts where multiple actors—organisations, individuals, groups—each contribute to effects seen at system level, but it remains difficult to hold any single actor responsible for these effects. Efforts by individual actors, including local quality improvement (QI) projects, may have the paradoxical effect of undermining system safety. Many challenges cannot be resolved by individual organisations, since they require whole-sector coordination and action. We call for recognition of the problem of many hands and for attention to be given to how it might most optimally be addressed in a healthcare context.