Clostridium acetobutylicum has received renewed interest worldwide as a promising producer of biofuels and bulk chemicals such as n-butanol, 1,3-propanediol, 1,3-butanediol, isopropanol, and butyrate. To develop commercial processes for the production of bulk chemicals via a metabolic engineering approach it is necessary to better characterize both the primary metabolism and metabolic regulation of C. acetobutylicum. Here, we review the history of the development of omics studies of C. acetobutylicum, summarize the recent application of quantitative/integrated omics approaches to the physiological analysis and metabolic engineering of this bacterium, and provide directions for future studies to address current challenges. Systems biology tools for C. acetobutylicum have developed rapidly in the last few years with an emphasis on quantitative analysis.It is now possible to determine the number of mRNA molecules per cell as well as the number of protein molecules per cell for most of the genes encoding enzymes involved in the central metabolism.Quantitative omics tools have been used to characterize the central metabolism of C. acetobutylicum and the regulation of this metabolism under different physiological conditions.Several metabolic mutants have been characterized using quantitative omics tools, providing an understanding of the metabolic flexibility of C. acetobutylicum at the molecular level.Construction of industrial C. acetobutylicum mutant strains for the production of bulk chemicals benefits from the quantitative omics tools that are now available