Strain-specific hypersensitive (HR) and extreme resistance (ER) phenotypes elicited in potato plants by three Potato virus Y (PVY) isolates in strain groups PVYO (BL and DEL3) and PVYD (KIP1) were studied. PVYO and PVYD isolates elicit HR genes Ny or putative Nd, respectively, and all three isolates elicit ER gene Ry. They were inoculated to 39Australasian, European, orNorth American potato cultivars released over a 117-year period and harvested tubers were replanted. Both primary and secondary symptoms were recorded. Two European cultivars always developed ER following sap and graft inoculation and, thus, carried comprehensive PVY resistance gene Ry. One Australasian and two European cultivars always developed susceptible phenotypes and, thus, lacked genes Ry, Ny, and putative Nd. Sap inoculation with isolate KIP1 elicited localized HR (LHR) in 31 cultivars and both LHR and systemic HR (SHR) in three others; thus, all carried putative Nd. Isolates BL and DEL3 both elicited susceptible phenotypes in 11 of these 34 cultivars but LHR alone, SHR alone, or both LHR and SHR in the other 23 which, therefore, all carry Ny. With these two isolates, SHR expression ranged from very severe to very weak, with the greatest numbers of isolate-cultivar combinations occurring in the severe category with BL (n = 11) andmoderate category (n = 12) with DEL3. Within the same isolate-cultivar combination, overall, SHR symptom expression was weaker with secondary than primary infection. With both primary and secondary infection, SHR expression was most severe with KIP1 and weakest with DEL3. Genes Ny and putative Nd were present in cultivars released between 1939 and 2010 or 1893 and 2010, respectively, occurring in cultivars from all three world regions. These findings have important implications concerning breeding new PVY-resistant potato cultivars, especially for countries lacking healthy seed potato stocks, or where subsistence farmers cannot afford them. An alternative to including gene Ry is incorporating as many strain-specific PVY resistance genes as possible.