Abstract In reaction to a stimulus, signaling molecules are made, generate a response, and are then degraded. Nucleotides are classically associated with central metabolism and nucleic acid biosynthesis, but there are a number of nucleotides and nucleotide derivatives in plants to which this simple definition of a signaling molecule applies in whole or at least in part. These include cytokinins, chloroplast guanosine tetraposphate (ppGpp), as well as extracellular canonical nucleotides such as extracellular adenosine triphosphate (eATP) or nicotinamide adenine dinucleotide (eNAD+). In addition, there is a whole series of compounds derived from NAD+ such as adenosine diphosphate (ADP) ribose (ADPR), ATP-ADPR dinucleotides and their hydrolysis products (e.g. pRib-AMP) as well as different variants of cyclic ADPR (cADPR, 2'-cADPR, 3'-cADPR). Furthermore, cyclic nucleotides such as 3',5'-cAMP or 2',3'-cyclic nucleoside monophosphates. Interestingly, some of these compounds have recently been shown to play a central role in pathogen defense. In this review, we highlight these exciting new developments. We also review nucleotide derivatives that are considered candidates for signaling molecules, for example purine deoxynucleosides, for which the evidence base is still rather thin, and discuss more controversial cases.