Recent alternatives to technological applications most commonly employed when the production of extremocompounds is approached at bioreactor scale, in batch, fed-batch, and continuous mode, are summarized. Each operational mode is analyzed in the light of the more decisive variables affecting the performance of this kind of biological processes, namely, bioreactor configurations, culture medium design, operating conditions, or downstream processing. Bringing together genetic and bioreaction engineering with separation techniques is already the recommended strategy to solve the typical problems faced in bioprocesses with extremophiles and will serve to open up new opportunities for the development of unexplored fields such as renewable energies.