Many brown rot fungi are capable of tolerating high levels of copper. Since these fungi are not controlled by copper alone, copper-based wood preservatives typically contain a broad spectrum fungicide that protects wood from these destructive fungi. Replacing the broad-spectrum fungicide with one that targets the copper-tolerant fungi would be more environmentally friendly and sustainable, but, unfortunately, none exist at present. Using genome-wide gene expression data, Forest Service researchers found three linked biochemical pathways to be essential for growth of these fungi on copper-treated wood. Pyraclostrobin, a fungicide that blocks one of these biochemical pathways, was tested in decay studies to determine its efficacy. Results from laboratory studies were promising. The combination of copper and pyraclostrobin was at least as effective as the reference, a commercially sold copper-based wood preservative treatment. With more than 19 classes of fungicides and over 150 active ingredients currently on the market, it is clear that a rational approach based on the biological understanding of wood decay will greatly speed the discovery of new targeted biocides for wood protection.