Few argue with the need for modeling and simulation (M&S) to better or more completely represent current and expected military operations. The challenge is to decide where to make specific improvements in M&S representation and functionality within time, funding, technology, and research limitations. So, it is natural to select key areas - Grand Challenges - for a significant evolution in M&S where a major effort of many at considerable cost is needed to deal with the critical issues ahead. This paper selects three proposed and related Grand Challenges. First, M&S Depiction of Information and Effects-Based Operations, as a Grand Challenge, will assist in creating sufficiently realistic battlespaces for M&S users. Second, M&S Support to Crisis Response and Military Operations, as a Grand Challenge, is a key area that will help the Department of Defense meet transformation goals. Third, Effective Development of Future Simulations, as a Grand Challenge, will set the standards by which future M&S improvements and new M&S programs will be acquired to ensure needed simulations are delivered on time and at desired cost.