Plants perceive environmental changes in one tissue and inform distant tissues of these changes using long-distance signals. These signals are implicated in developmental processes such as the transition to flowering as well as in responses to abiotic and biotic stresses, including pathogen infection and herbivory. In this review, we discuss research findings in the regulation of flowering time as well as in induced defense responses from the perspective that long-distance signaling progresses in a series of distinct stages: (1) initiation or induction, (2) synthesis and movement of a signal to distant tissues, (3) perception of the signal, and (4) establishment or manifestation of the appropriate response. We highlight recent studies that implicate DIR1 and lipids, methyl salicylate, and jasmonic acid (JA) as long-distance signals during systemic acquired resistance (SA R). Additionally, it appears that a requirement for JA is common to the SAR, induced systemic resistance, and wound response pathways. Finally, we discuss future avenues of research to further elucidate the mechanisms of long-distance signaling in plants.