Among various contaminants, ozone (O 3 ) is considered the most ubiquitous and phytotoxic atmospheric pollutant in industrialized and developing countries. It causes extensive risks for plant life, in terms of survival and productivity of wild and cultivated species. Plant response to O 3 resembles the biotic defense reactions and includes two steps: the first is a biphasic oxidative burst with a massive, rapid, and transient increase in apoplastic reactive oxygen species (ROS) production; the second is the induction of the hypersensitive response (HR) and systemic acquired resistance (SAR). In particular, the acute O 3 exposure (high concentrations for a few hours) results in the activation of programmed cell death (PCD) response that interacts with the synthesis of several hormones and other signaling molecules. The cross talk among all these molecules and their complex and interconnected signaling pathways are more important to determine (1) the initiation, propagation, and containment of O 3 -induced cell death, (2) the degree of the sensitivity of plants to this contaminant, and (3) the regulatory potential that plants have to promptly respond to oxidative stress. The present chapter reviews the role of phytohormones (such as ethylene, abscisic acid, gibberellins, auxins, and cytokinins) and other signaling molecules (such as salicylic and jasmonic acids, proline, and brassinosteroids), as well as their synergistic and antagonistic effects, in the complex signaling pathway involved in plant responses to O 3 stress.