This work is the result of the convergence of the research in biochemical reaction engineering and metabolic flux analysis for serine alkaline protease (SAP) production. The genus Bacillus includes a variety of industrially important species that are known to secrete a large number of extracellular proteases and are used among many species as producer of SAP enzyme. Therefore, in the first part of the present article an overview to serine alkaline protease and regulation of its synthesis and secretion in Bacillus is presented. In the second part, a detailed review of the published information on the bioprocess medium design and bioreactor operation parameters are discussed in relation to the concentrations of the byproducts, i.e. neutral protease, amylase, amino acids, organic acids and alcohols. In the third part, papers on metabolic flux analysis for SAP are reviewed with the emphasis on SAP overproduction potential of the Bacillus licheniformis, the effect of oxygen transfer on the bioreaction-network fluxes and the need for oxygen transfer strategies. The metabolic bottlenecks and strategies for increasing the yield and selectivity of SAP fermentation process are discussed.