Despite a rich history of etiological research, the field of occupational safety and health does not have a rigorous history of research on what works and does not work to prevent and control occupational diseases and injuries. National and global transformations of economies and workplaces with enhanced competitiveness require more attention to options for interventions. A three-pronged approach to building a body of knowledge on intervention research in occupational health and safety is identified in this paper. The approach focuses on the science, skills, and strategies that can be useful in intervention research. Scientifically, researchers can draw on constructs and techniques from epidemiology, evaluation practice, and clinical trials. Experimental and nonexperimental approaches have value for occupational studies. The skills needed represent a range of disciplines beyond those traditional of health and safety; social scientists, economists, and organizational theorists often need to be part of research teams. Strategic approaches involve more labor-management partnerships, prospective study designs, and the use of intermediate and surrogate indicators. The strategic challenge will be to conduct intervention research against a backdrop of overriding political and economic pressures.