Biotic stresses significantly limit global crop production. Identification and use of resistant cultivars is currently seen as the best strategy, cheapest, durable and environmentally friendly method to manage biotic stresses. However, resistance gained through single gene/quantitative trait loci (QTLs) transfer leads to resistance breakdown within a short period. Hence, current breeding programs targeted at developing durable and/ broad spectrum resistant cultivars by pyramiding multiple resistant genes/QTLs. Despite its significant contributions to crop improvement, gene pyramiding through conventional breeding suffers from being laborious, time consuming, costly and less efficient. Recently, the use of modern molecular tools like molecular markers and genetic engineering has dramatically enhanced the gene pyramiding strategy for biotic stress resistance. Molecular markers are very helpful for precise identification, mapping and introgression of multiple desirable genes/QTLs underlying trait of interest. Moreover, Genetic engineering has enabled scientists to transfer novel genes from any source into plants in a single generation to develop cultivars with the desired agronomic traits. Therefore, the current paper targeted to review the different types of biotic stress resistance in plants and the methodologies for identification, mapping and pyramiding of resistance genes/QTLs to develop durable and/or broad spectrum biotic stress resistant cultivars. So far, numerous crops with durable/broad spectrum resistance to pathogens, insect pests and herbicides have been developed by pyramiding multiple resistant genes/QTLs using marker assisted selection and genetic engineering techniques to contribute to increased crop production and productivity to maintain food security globally.