Over the past century, advances in analytical chemistry have played a significant role in understanding wine chemistry and flavor. Whereas the focus in the 19th and early 20th centuries was on determining major components (ethanol, organic acids, sugars) and detecting fraud, more recently the emphasis has been on quantifying trace compounds including those that may be related to varietal flavors. In addition, over the past 15 years, applications of combined analytical and sensory techniques (e.g., gas chromatography-olfactometry) have improved the ability to relate chemical composition to sensory properties, whether identifying impact compounds or elucidating matrix effects. Many challenges remain, however. This paper discusses some of the recent research aimed at understanding how viticultural and enological practices influence grape and wine volatiles. In addition, the challenges in linking composition to sensory properties will also be reviewed. Finally, future advances in linking grape, yeast, and human genomics to wine chemistry and flavor will be briefly discussed.