Studies on the molecular mechanisms of microbial adaptation in chaotropic and low water activity (aw) environments are poorly understood. Chaotropic environments are characterized as salt rich, MgCl2 and CaCl2, which lowers the availability of water for biological processes. PATRIC, an integrated genomic browsing tool containing vast libraries of sequenced genomes, can help us identify unique genetic markers in chaophilic and xerophilic microbes. Halophilic microbes are characterized as obligate hypersaline with the ability to tolerate exposure to chaotropic agents. Microbes with the greatest tolerance in these extreme environments must have advanced adaptive methods. Halobacterium salinarum and Haloquadratum walsbyi are chaotolerant and well adapted to low water activity. Haloquadratum walsbyi is unique among the halophilics as having the highest tolerance for chaotropes and its square shape. Performing comparative genomics using fully sequenced halophilic archaea such as Halobacterium salinarum NRC-1, a model halophile, and Haloquadratum walsbyi C23, we were able to identify genes that confer adaptation to chaotropic and low aw environments, as well as individual adaptations that may be responsible for the varying levels of tolerance in chaotropic environments . Characterizing genes associated with chaotolerance and low aw adaptations can help elucidate the cellular functions that make these microbes unique. Chaotropic brines may be used as analogs to study the origin of life and the possibility of suitable environments hosting extremophilic microbes on other planets like the Martian brines and the icy moons of Europa; therefore, studying the microbiome of chaotropic environments are essential in the field of astrobiology.