Earth System Models have become a holy grail of the earth sciences. Earth System Models are a class of simulation that model a significant number of interactions between the atmosphere, the oceans, the land, the cryosphere, and the biogeochemical cycles. Such models are an evolution of climate and physical ocean models developed for disciplinary purposes and of the land surface models that have developed from ecology and hydrology. Increasingly they also include some components of the carbon cycle, ecosystems, and atmospheric photochemistry. The development of a new class of models successfully capturing the behavior of a system is itself a demonstration of a certain level of scientific knowledge. However, the development of Earth System Models has been strongly forced by a series of important scientific questions. Of special interest are questions coupling forcing (atmospheric greenhouse gases) and response (climate and ocean circulation). The carbon cycle is the best understood of the major global biogeochemical cycles, and so I focus on issues linked to carbon; however, the next generation of challenges will grow and include the nitrogen, ozone, sulfur, and iron cycles. In this chapter, I discuss some emerging questions and identify some key research areas associated with these new areas of inquiry.