During their lifetime, plants need to adapt to various stimuli originating from the abiotic and biotic environment. One major biotic stress factor is the attack of herbivorous insects feeding on the plant. During the feeding process wounding of plant tissue and contact with elicitors in insect’s oral secretion (OS) occurs. The early events upon perception of these stimuli are still poorly understood. Elevations in cytosolic calcium are one of these early events, which activate the downstream signaling network. To reach this a proper decoding of calcium signals is important. In this study it was demonstrated that in Arabidopsis thaliana, several members of the calmodulin-like proteins (CMLs), one group of calcium sensors, are induced upon OS of the generalist herbivore Spodoptera littoralis. In herbivory, CML37 is strongly upregulated upon mechanical wounding, but responds additionally to elicitors in OS. Upon stress stimuli, CML37 binds to cytosolic free calcium and undergoes conformational changes. Mutation of CML37 increases plants susceptibility to herbivore feeding indicating that CML37 acts as a positive defense regulator. Beside herbivore defense, CML37 is also involved in ABA signaling during drought stress where mutation of CML37 results in drastically reduced survival of plants. Plant defense is a complex network of different pathways. Next to the jasmonate pathway, also the accumulation of γ-amino butyric acid (GABA) is calcium-mediated. Upon elevation of cytosolic calcium and binding by calmodulin (CaM), the glutamate decarboxylases (GADs) are activated and GABA produced. It was demonstrated that GABA is accumulated upon wounding of plant tissue and Spodoptera littoralis feeding. Higher level of GABA in a mutant or in artificial diet significantly reduced growth of Spodoptera littoralis larvae showing that herbivore-induced accumulation of GABA is a wound-induced, JA-independent and systemic plant defense.