The discovery of life in seemingly prohibitive environments continues to challenge conventional concepts of the growth-limiting conditions of many cellular organisms. The diversity of extremophiles has barely been tapped -estimates generally agreeing that <1% of the microorganisms in the environment have been cultivated in pure cultures to date. The production of extremophilic biomass is very important to provide sufficient material for enzyme and biomolecule isolation and characterization, eventually revealing particular features of industrial interest. Hence, special equipment and custom-tailored processes have been developed and are currently under evaluation for the improvement of fermentation productivity. Despite the remarkable opportunities that these uncommon organisms present for biotechnological applications only few instances can be reported for actual exploitation. This lack of progress from the research findings at a laboratory-scale to the actual development of pilot and large-scale production is correlated with the difficulties encountered in extremophile cultivations. Here, we report recent achievements in the production of biomass and related enzymes and biomolecules from extremophile sources, especially focusing on the application of novel fermentation strategies.