Workplace safety does not exist in a vacuum. Individuals come to work with a variety of advantages and disadvantages derived from their off-work activities. Extra-workplace behaviors and attitudes are likely to have greater impact for lone workers because such workers typically operate under less formal and informal oversight and receive less workplace support. The Total Worker HealthTM (TWH) approach, advocated by the National Institute for Occupational Safety and Health (NIOSH) in the USA, integrates traditional safety and health protection within a broader health promotion focus that acknowledges interactions between health and well-being and workplace injuries. The current paper outlines features of the TWH approach and summarizes TWH interventions recently developed for truck drivers and home care workers. With this background, opportunities for the development of TWH interventions for Irish lone workers are considered.