Nineteen single dominant genes (R genes) for resistance to viruses, nematodes, and fungi have been positioned on the molecular map of potato using DNA markers. Fourteen of those genes are located in five "hotspots" for resistance in the potato genome. Quantitative trait loci (QTL) for resistance to late blight caused by the oomycete Phytophthora infestans, to tuber rot caused by the bacterium Erwinia carotovora ssp. atroseptica, and to root cyst nematodes have been identified on all 12 potato chromosomes. Some QTL for resistance to different pathogens are linked to each other and/or to resistance hotspots. Based on the genetic clustering with R genes, we propose that some QTL for resistance have a molecular basis similar to single R genes. Mapping potato genes with sequence similarity to cloned R genes of other plants and other defense-related genes reveals linkage between candidate genes, R genes, and resistance QTL. To explain the molecular basis of polygenic resistance in potato we propose (a) genes having structural similarity with cloned R genes and (b) genes involved in the defense response. The "candidate gene approach" enables the identification of markers highly useful for marker-assisted selection in potato breeding.