Healthcare systems across the world and especially those in low-resource settings (LRS) are under pressure and one of the first priorities must be to prevent any harm done while trying to deliver care. Health care workers, especially department leaders, need the diagnostic abilities to identify local safety concerns and design actions that benefit their patients. We draw on concepts from the safety sciences that are less well-known than mainstream quality improvement techniques in LRS. We use these to illustrate how to analyse the complex interactions between resources and tools, the organisation of tasks and the norms that may govern behaviours, together with the strengths and vulnerabilities of systems. All interact to influence care and outcomes. To employ these techniques leaders will need to focus on the best attainable standards of care, build trust and shift away from the blame culture that undermines improvement. Health worker education should include development of the technical and relational skills needed to perform these system diagnostic roles. Some safety challenges need leadership from professional associations to provide important resources, peer support and mentorship to sustain safety work.