Beneficial soil-borne microorganisms can induce an enhanced defensive capacity in above-ground plant parts that provides protection against a broad spectrum of microbial pathogens and even insect herbivores. The phytohormones jasmonic acid (JA) and ethylene emerged as important regulators of this induced systemic resistance (ISR). ISR triggered by plant growth-promoting rhizobacteria and fungi is often not associated with enhanced biosynthesis of these hormones, nor with massive changes in defense-related gene expression. Instead, ISR-expressing plants are primed for enhanced defense. Priming is characterized by a faster and stronger expression of cellular defense responses that become activated only upon pathogen or insect attack, resulting in an enhanced level of resistance to the invader encountered. Recent advances in induced defense signaling research revealed regulators of ISR and suggest a model in which (JA)-related transcription factors play a central role in establishing the primed state.