The informal workforce is growing worldwide, and changes in the global structure of employment and in places of employment mean that work is a source of hazard and ill-health for many poorer workers. Yet informal workers do not have access to work-related social security. They face high work-related risks, but have little or no access to reliable formal or informal social protection. Citizen-focused social security programmes, such as cash transfers, do not give enough attention to the needs of able-bodied adults who work. Further, informal workplaces are not covered by the traditional discipline and practice of occupational health and safety (OHS), which is a necessary component of overall work-related social security. In particular, poorer informal workers are ill-placed to make use of possible preventive interventions, as they may lead to loss of income in the short term. A more inclusive approach will require changes in the institutional arrangements governing OHS, and should involve especially local authorities and informal worker organizations, who are developing influential international sectoral networks. In this regard, promising examples of negotiated and inclusive OHS policy reforms are presented. The broader challenge is to develop an expanded OHS that specifically includes informal workers as “workers”, rather than as “vulnerable citizens” who qualify only for poverty-oriented social protection programmes, and that explicitly addresses preventive measures.