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Systemic acquired resistance (SAR) is an evolutionarily conserved defense mechanism induced in the distal parts of plants after a locally restricted primary infection. It confers a long-lasting protection against a broad spectrum of microbial pathogens. Salicylic acid (SA) and N-hydroxy-pipecolic acid (NHP) function as signal molecules in SAR as well as in the local defense responses. We use a combination of different metabolomics workflows together with transcriptomics and autoimmunity mutants to identify missing steps in NHP and SA homeostasis. Thereby we have identified so far three main regulatory steps during previous years. SAR Deficient 4 (SARD4) as a ketimine reductase that converts the product of AGD2-LIKE DEFENSE RESPONSE PROTEIN1 (ALD1) into pipecolic acid. avrPphB SUSCEPTIBLE3 (PBS3) catalyzes the formation of isochorismate-9-glutamate as missing link towards SA biosynthesis and the glycosyltransferase UGT76B1 as a critical regulator for plant immunity as it governs the homeostasis of NHP. Together we believe that the combination of different metabolomics technologies and reverse genetic screens stimulates research in the field of plant immunity.