To improve microbial fermentation as an efficient way to sustainably produce green chemicals from renewable resources, novel production organisms are being explored. Extremophiles, in general, and moderate thermophiles in particular, offer important advantages over well-known mesophilic biotechnology hosts, such as Escherichia coli and Saccharomyces cerevisiae. These advantages include robust performance at temperatures that allow high substrate and product solubility, decreased contamination risk and growth conditions that match with the optimal conditions for enzymes used in saccharification processes, allowing efficient simultaneous saccharification and fermentation. In this review we will evaluate the use of extremophiles for the production of bio-based chemicals, with the main focus on the potential of these organisms for efficient production of bulk products such as platform chemicals. Examples include the application of thermophilic Bacillus and Clostridium species for organic acid production. Furthermore, we will discuss the development of genetic tools for biotechnologically-relevant extremophiles, as this is crucial for optimizing their specific production capacities, as well as for developing them as industrial platform organisms.