Muscadine grapes contain high concentration of polyphenols that are known to be involved in plant defense. Resveratrol encoded by stilbene synthase (STS) is one of the important phenolic compounds found in muscadine grape that has antimicrobial activity as well as health benefit. Cloning and sequencing of STS from muscadine revealed six isoforms of stilbene synthase genes, of which four were found to be different from that of V. vinifera STS sequence (BS). Rapid Amplification of cDNA Ends (RACE) to one of the muscadine stilbene synthase cDNA (MSB1) sequence also showed sequence variation with V. vinifera STS. The expression level ofMSBl and BS gene in anthracnose- tolerant muscadine cultivar was analyzed and confirmed through real time PCR after challenging the grape plants with the fungus Elsinoe ampelina. The expression of MSBl was found to be higher in muscadine compared to V. vinifera confirming that the muscadine genotypes may possibly have the potential to synthesize sufficient amount and type of stilbene phy to alexins to defend against pathogen attack.