Extremophiles are organisms that can thrive under extreme environmental conditions. There are many types of extremophiles, which require different growth conditions and habitats to grow; among them are the halophilic and the halotolerant microbes. These microbes are reported to grow in habitats of high salinity regions including the sea, sediments, lakes, mines, plant and the soil. They need high carbon source and salt concentration to achieve maximum tolerable condition for their survival.  High salinity survival and tolerance of these microbes are mechanized due to their osmotic and ionic stress, which are regulated through their genetic expression of enzymes, proteins, cell wall compositions and transporters. Thus, due to their robustness; the halophiles and halotolerant fungi showed high potential in health care; antimicrobial and anticancer activity, nanoparticle synthesis, enzyme production, genetics, bioremediation and other aspects. The aim of the current study was to explore the halophilic and halotolerant fungi, which are least explored for their habitats, growth requirements, and mechanism for salt resistance and tolerance. This will be followed by their biotechnological applications focusing on the biomedical industry, due to the emergence of the new multi-drug resistant pathogenic microbes.