It is estimated that burn injury affects about 1 in 3000 people annually world-wide. Burn injury induces severe pain, which is difficult to control in the great majority of cases making burn injury-associated pain a serious clinical challenge. In order to meet this clinical need, novel targets should be identified. Like pain developing in other peripheral pathologies, burn injury-associated pain is also initiated and maintained by signalling between the injured tissues and primary sensory fibres that supply those tissues. This signalling is underlain by the formation and accumulation of a mixture of agents at the site of the injury, some of which could be targets for intervention. However, at present the composition of this “burn injury tissue fluid” is incompletely established. Here, we summarise our current understanding of the composition of this burn injury tissue fluid and explore how already known agents in that tissue fluid may activate nociceptors to initiate and maintain pain associated with burn injury.