SummaryIn stark contrast to Arabidopsis, a related species, Thellungiella halophila (Thellungiella salsuginea; salt cress), displays extreme tolerance to high salinity, low humidity and freezing. High nucleotide sequence identity permits the use of tools developed for Arabidopsis for Thellungiella transcript profiling, for which a microarray platform with >25 000 DNA elements (70‐mer oligonucleotides) was used. Microarray transcript profiling and intensity analysis, quantitative RT‐PCR, and metabolite profiles define genes and pathways that showed shared and divergent responses to salinity stress in the two species. Shared responses are exemplified by 40% of the regulated genes functioning in confining ribosomal functions, photosynthesis and cell growth, as well as activating osmolyte production, transport activities and abscisic acid‐dependent pathways. An additional 60% of regulated genes distinguished Thellungiella from Arabidopsis. Analysis of the differences showed that Arabidopsis exhibited a global defense strategy that required bulk protein synthesis, while Thellungiella induced genes functioning in protein folding, post‐translational modification and protein redistribution. At 150 mm NaCl, Thellungiella maintained unimpeded growth. Transcript intensity analyses and metabolite profiles supported the microarray results, pointing towards a stress‐anticipatory preparedness in Thellungiella.