Susceptible Vitis vinifera responds to Xylella infection with a massive redirection of gene transcription. This transcriptional response is characterized by increased transcripts for phenlypropanoid and flavonoid biosynthesis, ethylene production, adaptation to oxidative stress, and homologs of pathogenesis related (PR) proteins, and decreased transcripts for genes related to photosynthesis. In addition, the results suggest that susceptible genotypes respond to Xylella infection by induction of limited, but inadequate, defense response. We also compared the transcriptional and physiological response of plants treated by pathogen infection, low or moderate water deficit, or a combination of pathogen infection and water deficit. Although the transcriptional response of plants to Xylella infection was distinct from the response of healthy plants to moderate water stress, we observed synergy between water stress and disease, such that water stressed plants exhibit a stronger transcriptional response to the pathogen. This interaction was mirrored at the physiological level for aspects of water relations and photosynthesis, and in terms of the severity of disease symptoms and pathogen colonization, providing a molecular correlation of the classical concept with the disease triangle.