Extremophilic prokaryotes, inhabitants of hot, cold, acidic, alkaline, saline, and deep-sea ecosystems, are classified as mono- and polyextremophilic or extreme-tolerant. Under conditions of heating, acidification, or salinization, thermophilic saprotrophic archaea are capable of maintaining endogenous homeostasis and high growth rates by biosynthesis of heat shock enzymes (proteins ofgeneral stress response), C40C40 membrane tetraesters with different numbers of cyclopentane rings, trehalose, and other hyperosmolytes. Small size of reduced genomes (0.5–3.0 Mb) of archaeal thermoacidophiles and hyperthermophiles was shown to reflect their adaptability mainly due to phenotypic changes and probably to have a reduced potential for speciation. In contrast, psychrophilic heterotrophic bacteria respond to sublethal temperature decrease by increased conformational flexibility of the macromolecules and elevated content of unsaturated fatty acids in the composition of their membrane lipids, synthesize membrane-associated glycoproteins, anti-freeze proteins, a group of general stress response proteins, specific and inducible cold shock proteins, which increase the growth rate. When slowing down and stopping the growth, psychrophiles switch on the processes of secondary metabolism and sharply increasing the biosynthesis of adaptogenic exopolysaccharides. Thus, they ameliorate the direct effects of salinity and hydrostatic pressure on viable cells, block the viral attack, and affect the microstructure and physicochemical properties of ice. Marine psychrophilic and piezopsychrophilic bacteria havelarger genomes of 2.6–6.4 Mb, which reflects their adaptability due to genotypic changes and an increased potential for speciation.