Prevention efforts, especially in high-income countries, have reduced work-related death and injury. Despite this, the global incidence of workplace fatalities remains unacceptably high with approximately 317 million incidents occurring on the job annually. Of particular concern is the occurrence and re-occurrence of incidents with a similar cause and circumstance, such as fatalities occurring in agriculture and transport industries. Efforts to reduce workplace fatalities include surveillance and reporting, investigation, and regulation. Challenges remain in all three domains, limiting the prevention of work-related injuries and deaths. In this commentary, the nature of these challenges and recommendations on how to overcome them are described. Examples of incidents of workplace injury and death, as well as injury prevention efforts are provided to ensure contextual understanding. Reflecting on the present enhances key stakeholders, policy and decision-makers' understanding of the opportunities to reducing harm and the associated human, and economic and legal costs.