The anthropocentric term "extremophile" was introduced more than 30 years ago to describe any organism capable of living and growing under extreme conditions—i.e., particularly hostile to human and to the majority of the known microorganisms as far as temperature, pH, and salinity parameters are concerned. With the further development of studies on microbial ecology and taxonomy, more "extreme" environments were found and more extremophiles were described. Today, many different extremophiles have been isolated from habitats characterized by hydrostatic pressure, aridity, radiations, elevated temperatures, extreme pH values, high salt concentrations, and high solvent/metal concentrations, and it is well documented that these microorganisms are capable of thriving under extreme conditions better than any other organism living on Earth. Extremophiles have also been investigated as far as the search for life in other planets is concerned and even to evaluate the hypothesis that life on Earth came originally from space. Extremophiles are interesting for basic and applied sciences. Particularly fascinating are their structural and physiological features allowing them to stand extremely selective environmental conditions. These properties are often due to specific biomolecules (DNA, lipids, enzymes, osmolites, etc.) that have been studied for years as novel sources for biotechnological applications. In some cases (DNA polymerase, thermostable enzymes), the search was successful and the final application was achieved, but certainly further exploitations are next to come.