Plant stilbenes are a small group of phenylpropanoids, which have been detected in at least 72 unrelated plant species and accumulate in response to biotic and abiotic stresses such as infection, wounding, UV-C exposure and treatment with chemicals. Stilbenes are formed via the phenylalanine/polymalonate-route, the last step of which is catalysed by the enzyme stilbene synthase (STS), a type III polyketide synthase (PKS). STSs are closely related to chalcone synthases (CHS), the key enzymes of the flavonoid pathway, as illustrated by the fact that both types of enzymes share a high amminoacidic omology, the same crystallographic structure and even the same substrates. STS genes appear to exist as a family of closely related genes in the majority of stilbene producing plant species. Also CHS genes are organized in a small family in grapevine, comprising three members (CHS1, CHS2 and CHS3). In this study a complete characterization of the grapevine STS multigenic family has been performed, in order to shade light on its controversial size based on predictions obtained from the two sequenced genomes now available. The analysis has been coupled with a comprehensive set of gene expression analyses on both the PKS families (CHS and STS) including healthy tissues at differential developmental stages and leaves exposed to both biotic (downy mildew infection) and abiotic (wounding and UV-C exposure) stresses. At least thirty-three full length sequences encoding VvSTS genes were identified, which, based on predicted amino acid sequences, cluster in 3 principal groups designated A, B and C. The majority of VvSTS genes cluster in groups B and C and are located on chr16 whereas the few gene family members in group A, which are also the closest to the CHS scaffold, are found on chr10. Microarray and mRNA-seq expression analyses revealed different patterns of transcript accumulation between the different groups of VvSTS family members and between VvSTSs and VvCHSs. Indeed, under certain conditions the transcriptional response of VvSTS and VvCHS genes appears to be diametrically opposed suggesting that flow of carbon between these two competing metabolic pathways is tightly regulated at the transcriptional level. This study represents an overview of the expression pattern of each member of the STS and CHS gene families in grapevine under both constitutive and stress- induced conditions. The results strongly indicate the existence of a transcriptional sub- functionalization amongst VvSTSs and provide the foundation for further functional investigations about the role and evolution of this large gene family. Moreover, it represents the first study to clearly show the differential regulation of VvCHS and VvSTS genes, suggesting the involvement of transcription factors (TFs) in both the activation and repression of these genes.