Metabolic control analysis (MCA) has become what it is, largely because the special organization of living cells led to rather specific questions. These questions focused on the role of enzymes, genes, and, in subsequent generalizations, on well-defined process activities. With an emphasis on the work by Heinrich and co-workers, the theory behind MCA is summarized in a way that leads naturally to its extensions to hierarchical systems, such as gene expression and signal transduction, and to control beyond the steady state. The analysis of the control properties of signal transduction cascades is reviewed with an emphasis on the relative importance of the protein kinases and the protein phosphatases. The two types of enzyme are both important for the amplitude of signal transduction, whereas phosphatases may be more important for the later phases of signal transduction and for its duration. Novel MCA of concentrations and fluxes that vary with time is explicated. It is concluded that the clarity and operationality of concepts such as control strength (now control coefficient) plus the clear theoretical frameworks provided by Heinrich and colleagues, should enable us greatly to reduce the Babylonian confusion that could otherwise occur in the data deluges of Systems Biology. © 2007.