Salicylic acid is a phytohormone indispensable for plant immunity. Interactions between hosts and pathogens create selective pressures—a cycle whereby hosts evolve novel defenses and alarm systems while their pathogen counterparts evolve enhanced weaponry and stealth tactics. Not uncommonly, plants lose the war against pathogens and succumb to disease. If a plant does survive a pathogen attack, it may be left with battle scars that reduce vegetative growth and fruit yield and quality. Without question, human survival depends on the abilities of plants to defend themselves against and survive pathogen onslaughts. With an increased understanding of plant immunity, humans will gain the ability to modulate and augment plant defenses to minimize disease and yield losses. Arabidopsis thaliana thimet oligopeptidase (TOP) family TOP1 and TOP2 metalloendopeptidases bind salicylic acid and may, therefore, play critical roles in plant immunity. Our research demonstrates that TOP1 and TOP2 regulate hydrogen peroxide accumulation, programmed cell death intensity, and possibly chloroplast integrity during the hypersensitive response following infection by the hemibiotrophic bacterial pathogen Pseudomonas syringae. We hypothesize that TOP1 and TOP2 are central hubs in reactive oxygen species production and redox regulation, and, as such, may influence physiological responses during both abiotic and biotic stresses.