Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst) is an important disease of wheat (Triticum aestivum) in Nepal, which is a part of the Himalayas stretching over the North of Nepal, India, Pakistan, Bhutan and beyond. Wheat production plays a crucial role in food security of the marginal hill farmers of Nepal. Frequent epidemics of the rust have caused huge loss in farmer's field. Periodic monitoring during 1980-2008 showed that changes in virulence occurred during this period. The objective of this study was to evaluate Pst resistance and its effective genes in wheat genotypes. For this, trap nurseries, wheat stripe rust differentials, commercial cultivars and advanced breeding lines were tested under artificial epiphytotic and natural hot spots conditions during 2005 to 2010. Four genes (Yr5, Yr10, Yr15 and YrSp) consistently showed resistance to the prevailing races. The gene Yr9 and Yr27 in combinations with Yr18 were found effective. Other lines with combination of minor genes were also found effective. The genotypes Amadina, Kukuna, Tukuru, Kakatsi and Buck Buck widely used in breeding program were resistant. The cultivation of varieties WK1204, Gautam, Gaura and Dhaulagiri have ensured genetic diversity for the rust resistance and slowed down frequent occurrence of epidemics. The findings of these studies could help in developing effective varietal resistance program in the sub-continent.