The exceptional adaptations of extremophilic microbes permit them to thrive in a broad range of temperatures, which include hot hydrothermal vents to freezing polar regions. The genetic and metabolic adaptations of extremophilic microorganisms allow their survival in such extreme conditions. Thermophilic microbes are located in hot environments like hydrothermal vents and hot springs and have adaptations to endure temperatures above 45 °C and, in some circumstances, above 100 °C. They hold a variety of molecular and physiological adaptations to survive, such as a dedicated lipid membrane system that is resistant to heat and thermostable enzymes, etc. On the other hand, subzero ecosystems such as permafrost, deep-sea habitats, and polar ice caps are examples of the home of psychrophilic microbes. These psychrophilic microbes produce cold-active enzymes, antifreezing proteins that prevent the production of ice crystals, and cryo-protectants like trehalose and glycerol that protect cells from any harm during cycles of freezing and thawing under low temperatures. Moreover, unsaturated fatty acids present in the membrane also preserve membrane fluidity. Such amazing adaptations of thermophilic and psychrophilic microorganisms are discussed in this chapter, with an emphasis on the tactics that allow them to survive and proliferate in both high- and low-temperature environments.