Biotic stress is regarded as one of the important causes of global crop losses accounting for about 35% of the total food production. In order to prevent huge crop yield losses and to attain sustainable food production, it is highly essential to improve host plant defence against biotic stressors. Conventional breeding strategies to develop stress-tolerant crops are now being synergized by various biotechnological tools including molecular markers and omics-based approaches. Recently, the application of genomic and transcriptomic tools has paved way for better understanding of stress tolerance in model and non-model crops. This chapter covers the concept of biotic stress, its impact on crop production, host plant defence mechanism and recent research on crop biotic stress tolerance using high-throughput genomics and transcriptomics approaches. The advanced computational tools that aid for the analysis of omics big data are also summarized.