Systemic acquired resistance (SAR) is a form of broad-spectrum resistance induced in response to local infections that protects uninfected parts against subsequent secondary infections. SAR signaling requires two parallel branches, one regulated by salicylic acid (SA), and the other by pipecolic acid (Pip), azelaic acid (AzA) and glycerol-3-phosphate (G3P). AzA and G3P function downstream of the free radicals nitric oxide (NO) and reactive oxygen species(ROS). The non-protein amino acid Pip functions by increasing NO/ROS levels. During SAR, SA, Pip, AzA, and G3P accumulate in the infected leaves, but only a small portion of these is transported to distal uninfected leaves. Plants defective in NO, ROS, G3P, or SA biosynthesis accumulate reduced Pip in their distal uninfected tissues although they contain wild-type-like levels of Pip in their infected leaves. This in turn is associated with transcript levels of AGD2-LIKE DEFENSE RESPONESE PROTEIN1 (ALD1),which encodes an rate-limiting enzyme in the Pip biosynthetic pathway. Together, these data indicate that Pip functions upstream of free radicals and de novo synthesis of Pip in distal tissues is dependent on both SA and G3P.