A look back at the early literature on reactive oxygen species (ROS) gives the impression that these small inorganic molecules had a singular defined role, that of host defence in mammalian systems. However, it is now known that their roles also include a major part in cell signalling, in a broad range of organisms from mammals to plants. Similarly, a look back at papers on the proteins now thought to be involved in the perception of hydrogen peroxide (H2O2) will show that they too had defined functions assigned to them, completely independent to H2O2 signalling. These proteins have disparate roles, in ethylene perception or even major metabolic pathways such as glycolysis. However, the chemistry of H2O2 sensing dictates that the proteins have a commonality, with active thiol groups being potential ROS targets. The challenge now is to determine the full range of proteins which may partake in the role of H2O2 perception, and to determine the mechanisms by which the signal is transmitted to the next players in the signal transduction pathways.