Adequate detection of trans-resveratrol in wine is complicated by two factors: relatively low levels and interferences from matrix components. Here, we present two useful approaches to overcoming these issues depending on the instrumentation available. For HPLC–UV analyses, matrix peaks can be removed by microextraction using packed sorbent while simultaneously concentrating the trans-resveratrol peak by a factor of two. For LC–MS, the extracted ion chromatogram for the [M + H]+ analyte ion can be used to obtain specificity without prior extraction procedures.