The pyridine nucleotide nicotinamide adenine dinucleotide (phosphate) [NAD(P)] is a universal electron carrier that functions in metabolic reactions and intracellular signaling processes. Accumulating evidence indicates that NAD(P) also acts in the extracellular space. It has been shown in animals that necrotic cell death leads to passive release of cellular NAD(P) into the extracellular space, where it is either processed by ectoenzymes or perceived by potential cell-surface receptors, triggering outside-in signaling. We found in the model plant Arabidopsis thaliana that, upon wounding and bacterial infection, intracellular NAD(P) is released into the apoplast at concentrations sufficient for immune activation, that exogenous NAD(P) induces resistance to bacterial pathogens, and that depletion of extracellular NAD(P) [eNAD(P)] by expression of the human NAD hydrolase CD38 in the apoplast partially compromises systemic acquired resistance (SAR). Using both forward and reverse genetic approaches, we have identified a number of signalling components downstream of eNAD(P) including two cell-surface receptors that bind NAD(P) with high affinity. Mutations of the receptors not only reduce exogenous NAD(P)-induced immune responses, but also compromise plant basal immunity against bacterial pathogens. Interestingly, exogenously added NAD moves systemically and induces systemic immunity and mutations in one of the receptors also compromises SAR. These results indicate that eNAD(P) is a primary damage-associated molecular pattern that may function as a mobile SAR signal in plants. These results also suggest that exogenous application of NAD(P) and overexpression of the NAD(P) receptors are potential strategies for improving crop disease resistance. In this talk, we will present our findings in the context of the plant immune system and will compare the mechanisms utilized by plants and animals to process and/or perceive eNAD(P). Future research directions on eNAD(P) and its receptors in the laboratory will also be discussed.