You can't have a conversation of any substance concerning drug development without one or more of the industry's very public problems weaving its way into the conversation. Depending on who you are talking to, the focus can any of several different topic but they all come down to three questions: a) How can we avoid the high late-stage attrition rate? b) How can we do better risk detection and management early safety signals? c) How can we reduce the high cost of drug development? There are many areas that are being investigated to address these three issues; adaptive designs, decision theory, data mining, improved safety signal detection, being a few. Modeling and Simulation is a tool that cuts across all of these areas and supports each one in its actual application. In this roundtable I would like to consider practical examples of where modeling and simulation has been used some