Systemic acquired resistance (SAR) is typically activated in healthy systemic tissues of locally infected plants. Upon pathogen infection, a mobile signal travels through the vascular system to activate defense responses in distal tissues. Salicylic acid (SA) is an essential signal molecule for the onset of SAR, as it is required for the activation of a large set of genes that encode pathogenesis-related proteins (PRs) with antimicrobial properties. Induced systemic resistance (ISR) is typically activated upon colonization of plant roots by beneficial microorganisms. Like SAR, a long-distance signal travels through the vascular system to activate systemic immunity in above-ground plant parts. ISR is commonly regulated by jasmonic acid (JA)- and ethylene (ET)-dependent signaling pathways and is typically not associated with the direct activation of PR genes. Instead, ISR-expressing plants are primed for accelerated JA- and ET-dependent gene expression, which becomes evident only after pathogen attack. Both SAR and ISR are effective against a broad spectrum of virulent plant pathogens.