Extremophile land plants have evolved convergently to become tough survivors in harsh soil and climatic conditions, such as extremes of soil pH, temperature, drought, high salinity, heavy metals, high light intensity, and UV radiation. Thus, the extremophile plants hold the potential key to improving stress-resilience in crop plants in the face of global climate change and desertification. Moreover, extremophile plants also exhibit industrial importance, being the source of active pharmaceuticals, new fuels, and essential chemicals. Transcriptome analysis of extremophiles is a common approach towards discovering genes and molecular mechanisms for adaptation to stress apart from identifying the pathways responsible for the biosynthesis of commercially essential metabolites. Again, the current scenario inextremophile research ranges from the study of extremophile plant models, e.g., Arabidopsis lyrata, to various plants of economic and ecological significance. The genetic signatures obtained from the transcriptome libraries of these extremophiles are utilized towards their conservation by employing the genome-editing approaches apart from extending their applicability towards the introgression of abiotic tolerance traits into agronomically important crop plants. This chapter aims to summarize the recent transcriptome analyses of extremophile species from the Indian Thar desert and other extreme eco-regions of the world.