Regulations concerning the work environment, tools, and the performance of work are at their best based on scientific evidence. Existing European directives, European and North American standards, and recent guidelines with the potential to prevent musculoskeletal disorders, are either qualitative or semiquantitative. The exception is the NIOSH lifting guide, which is highly quantitative. Of the European directives and standards, few have been developed with the primary goal of preventing musculoskeletal disorders, whereas one North American standard and another suggestion for a standard have this specific aim. In a review of epidemiological studies on low-back, neck, shoulder, and upper extremity disorders, several physical load factors were identified as risk factors for the disorders. Many of these factors have been repeatedly identified, and for different types of outcomes of an anatomical area (e.g. pain, disc herniation, disc degeneration of the low-back or neck). However, quantitative exposure-response relationships between physical load factors and disorders based on field studies are largely unknown. Experimental studies have provided a multitude of potentially useful data. It is concluded that both well-designed epidemiological studies with quantitative assessments of physical work load and valid measurements of musculoskeletal disorders, and experimental studies are needed for the future development of regulation. To determine the role of experimental studies in regulation, it should be known to what extent fatigue and other short-term responses are precursors of disorders. Regulation should be directed especially towards factors that are likely to be causative for musculoskeletal disorders. Examples of such factors are sudden overload in manual handling activities, heavy physical work involving manual handling tasks, and vibration from tools. Guidelines that are acceptable and feasible can and should be developed. The effects of such guidelines on the occurrence of musculoskeletal disorders should be investigated.