Microbial physiology has traditionally played a very important role in both fundamental research and in industrial applications of microorganisms. The classical approach in microbial physiology has been to analyze the role of individual components (genes or proteins) in the overall cell function. With the progress in molecular biology it has become possible to optimize industrial fermentations through introduction of directed genetic modification - an approach referred to as metabolic engineering. Furthermore, as a consequence of large sequencing programs the complete genomic sequence has become available for an increasing number of microorganisms. This has resulted in substantial research efforts in assigning function to all identified open reading frames - referred to as functional genomics. In both metabolic engineering and functional genomics there is a trend towards application of a macroscopic view on cell function, and this leads to an expanded role of the classical approach applied in microbial physiology. With the increased understanding of the molecular mechanisms it is envisaged that in the future it will be possible to describe the interaction between all the components in the system (the cell), also at the quantitative level, and this is the goal of systems biology. Clearly this will have a significant impact on microbial physiology as well as on metabolic engineering.