Exposure of plants to high ozone concentrations causes lesion formation in sensitive plants. Plant responses to ozone involve fast and massive changes in protein activities, gene expression and metabolism even before any tissue damage can be detected. Degradation of ozone and subsequent accumulation of reactive oxygen species (ROS) in the extracellular space activates several signalling cascades, which are integrated inside the cell into a fine-balanced network of ROS signalling. Reversible protein phosphorylation and degradation plays an important role in the regulation of signalling mechanisms in a complex crosstalk with plant hormones and calcium, an essential second messenger. In this review, we discuss the recent advances in understanding the molecular mechanisms of ozone uptake, perception and signalling pathways activated during the early steps of ozone response, and discuss the use of ozone as a tool to study the function of apoplastic ROS in signalling.