The true burden (morbidity, mortality, disability, cost, pain, distress) of occupational and work-related diseases and injuries is unknown, and what is reported as burden is significantly underestimated. This underestimation affects the way decision-makers view investments in research and worker protection, which in turn has a substantial impact on national welfare and public health. To better describe the societal and individual burdens of occupational and work-related diseases and injuries, we propose an approach to gauge what is known about burden and where new assessments may be made. This approach consists of 4 elements to consider in burden assessments: (1) utilizing multiple domains, including the individual worker, the worker's family, the community in which the workplace is located, the employer, and society as a whole; (2) taking a broader view of the work-relatedness of disease and injury; (3) assessing the impact of the entire working-life continuum; and (4) applying the comprehensive concept of "well-being" as an indicator in addressing contemporary changes in the nature of work, the workplace, and the workforce. Further research on burden and enhanced surveillance is needed to develop these elements.