First responders provide a key link in the chain of survival – enhancing access to life-saving interventions prior to the arrival of the emergency services. Despite the rapid growth of first responder initiatives, more evidence is required on optimal system configuration and the impact of first responder systems on outcomes. The scope of this special issue includes descriptions of first responder systems (where not previously reported), papers exploring barriers and facilitators to their effective use, descriptions of novel use of technology to support or enhance first response, as well as evaluations of their effect on clinical outcomes. Initiatives from lower resource settings are encouraged to submit their approaches and solutions to run first responder systems.