Even though we have moved beyond the Industrial Age and into the Information Age, manufacturing remains an important part of the global economy.There is a need for the pervasive use of modeling and simulation for decision support in current and future manufacturing systems, and several challenges need to be addressed by the simulation community to realize this vision. First, an order of magnitude reduction in problem-solving cycles is needed. The second grand challenge is the development of real-time, simulation-based problem-solving capability. The third grand challenge is the need for true plug-and-play interoperability of simulations and supporting software. Finally, there is the biggest challenge facing modeling and simulation analysts today: that of convincing management to sponsor modeling and simulation projects instead of, or in addition to, more commonly used manufacturing system design and improvement methods such as lean manufacturing and six sigma.