Escherichia coli and Bacillus subtilis are the best studied among bacteria, archaea, and eukaryotic microorganisms. They stand for the two major groups of Gram-negative and Gram-positive bacteria. The first linkage maps of E. coli and B. subtilis were compiled in 1964 and 1980, respectively. After some decades, whole genome sequences of both organisms were completed in 1997 and the subsequent investigations dramatically expanded our understanding of their functional genomics. E. coli presents an excellent system for almost all the various fields of molecular microbiology. The lactose operon was elucidated first in this organism and the notion of the operon influenced most studies of gene expression in eukaryotes as well as in prokaryotes. To some extent as a result of this success, many scientists turned their attention from E. coli to eukaryotes, such as the fruit fly or tissue culture during the 1970’s, leaving behind the most difficult problems, such as cell division, which are in fact still unsolved. B. subtilis, on the other hand, attracted researchers’ attention first because it could be so readily transformed and then because of its spore forming ability, and kept it even after the 1970s. Sporulation starts with asymmetric cell division separating mother cell and spore cell, where gene expression is different in the two cell types. Molecular mechanisms of differential gene expression were elucidated in the early 1990s. Enthusiasm for the molecular biological study of B. subtilis came thus a quarter century after the wave of interest in E. coli. And yet, although they are the best studied among microorganisms, the mechanism of cell division remains a mystery even in E. coli and B. subtilis.