in Wiley InterScience (www.interscience.wiley.com).As the gas industry has developed, gas pipeline networks have evolved over decades into very complex systems. A typical network today might consist of thousands of pipes, dozens of stations, and many other devices, such as valves and regulators. Inside each station, there can be several groups of compressor units of various vintages that were installed as the capacity of the system expanded. The compressor stations typically consume about 3-5% of the transported gas. It is estimated that the global optimization of operations can save considerably the fuel consumed by the stations. Hence, the problem of minimizing fuel cost is of great importance. Consequently, the objective is to operate a given compressor station or a set of compressor stations so that the total fuel consumption is reduced while maintaining the desired throughput in the line. Two case studies illustrate the proposed methodology. Case 1 was chosen for its simple and small-size design, developed for the sake of illustration. The implementation of the methodology is thoroughly presented and typical results are analyzed. Case 2 was submitted by the French Company Gaz de France. It is a more complex network containing several loops, supply nodes, and delivery points, referred as a multisupply multidelivery transmission network. The key points of implementation of an optimization framework are presented. The treatment of both case studies provides some guidelines for optimization of the operating performances of pipeline networks, according to the complexity of the involved problems. V V C 2009 American Institute of Chemical Engineers AIChE J, 56: 946-964, 2010