CD1d-restricted NKT cells have been identified as an important component of the immune system that have the capacity both to augment beneficial host immunity and to prevent harmful autoimmunity. These cells have the ability to produce a wide variety of cytokines, including both proinflammatory and antiinflammatory cytokines that can have multiple different effects on the outcome of immune reactions. The discovery that these T cells are activated by specific recognition of glycolipids in the glycosylceramide family has led to new approaches to manipulate the pleiotropic functions of these cells. Here, we review the multiple activities that have been attributed to NKT cells in a variety of different disease models, and the current state of our understanding of the mechanisms that control the functional outcome of NKT cell activation.