An important aspect of decision-making is the need to make interpretations and predictions in the face of uncertain information. In this issue of Neuron, Yu and Dayan describe a model of the role of acetylcholine and norepinephrine in balancing top-down expectation and bottom-up sensory input in guiding behavior. The model builds from data on physiological effects of modulators regulating the balance of cortical feedback and thalamic input.