Cybernetic modeling involves the application of control-theoretic ideas to the modeling and analysis of biological systems. It relies upon optimal control heuristics that describe the system-wide aims and functions of metabolic regulation, and thus provides a teleonomic approach for dynamic modeling of metabolic pathways. Combining cybernetic control laws with concepts from metabolic pathway analysis has culminated in a comprehensive cybernetic modeling strategy, which has been previously lacking. The newly devised framework relies upon the simultaneous application of local controls that maximize the net flux through each elementary flux mode and global controls that modulate the activities of these modes to optimize the overall nutritional state of the cell. These modeling concepts are illustrated using a simple linear pathway and a larger network representing anaerobic E. coli central metabolism. The E. coli model successfully describes the metabolic shift that occurs upon deleting the pta-ackA operon that is responsible for fermentative acetate production. The model also furnishes predictions that are consistent with experimental results obtained from additional knockout strains as well as strains expressing heterologous genes. Because of the stabilizing influence of the included control variables, the resulting cybernetic models are more robust and accurate than their predecessors in simulating the network response to imposed genetic and environmental perturbations.