Potato (Solanum tuberosum L.) is among the most important upland crops cultivated for many end uses throughout Japan. Potatoes are consumed in different ways, such as table use, food processing, starch production, and others. At the same time, various cropping systems are adopted according to environmental conditions. Although potato-breeding programs in Japan are conducted by considering these demands, pest and disease resistance is one of the most important traits required for all modern cultivars. There are many pests and diseases affecting potato production in Japan, where conferring resistance against potato cyst nematodes, late blight, common scab, bacterial wilt, and viral diseases has become a main target of breeding. Artificial inoculation tests and cultivation in infested fields were traditionally conducted, in order to evaluate the levels of resistance among breeding materials. However, several DNA markers for pest and disease resistance genes have recently been developed for the selection of resistant genotypes. We have taken both approaches toward the selection of pest and disease resistant genotypes at each breeding step. This review introduces our approaches to develop new pest and disease resistant potato cultivars by using classical and molecular approaches.