Saline environments are one of the most common extreme habitats prevalent in this universe. They are of two primary types, ‘thalassohaline’ those which arose from seawater, with NaCl as the dominant salt; and ‘athalassohaline’ of non-seawater origin with different ionic compositions. Organisms from all domains of life have adapted themselves to thrive in environments with salinities ranging from normal to the saturation level. In particular, halophilic microorganisms have developed several adaptive mechanisms to cope up with osmotic stress. While halotolerant or moderate halophiles use efflux pumps, or accumulate neutral compatible solutes in the cytoplasm; extreme halophilic microorganisms accumulate potassium ions, a strategy called ‘salting-in’ to match the high ionic composition in the external environment. The later predominantly includes archaeal members, except the bacterium, Salinibacter ruber. The general adaptive features of halophilic microorganisms also help them to thrive under, and overcome other stressed conditions such as resisting antibiotics, heavy metals and ionic liquids. These microorganisms have wide physiological diversities and include members of oxygenic and anoxygenic phototrophs, aerobic heterotrophs, and those capable of diverse anaerobic respiratory metabolisms. Nanomicroorganisms are also reported from saline environments. Their great metabolic versatility, low nutritional requirements, and adaptation machineries, make them promising candidates for several biotechnological applications such as production of pigments, biopolymers, compatible solutes, and salt tolerant hydrolytic enzymes. They are also used in bioremediation, food preservation, and preparation of specialized fermented foods. Understanding the halophiles also paves way for astrobiological research. This book chapter summarizes the present understanding of the diversity, adaptation, and application of halophilic microorganisms.