Although skill at gambling is usually thought to concern people frequenting casinos in Las Vegas, it has real-world consequences as well. Patients with orbitofrontal cortex (OFC) lesions show pronounced deficits in 'gambling' tasks, in which they are required to make choices based on the previous likelihood of monetary gain or loss—and it is widely thought that such deficits underlie their inability to use knowledge of more abstract reward or punishment to guide real-life behavior; such patients are frequently disinhibited, socially inappropriate and irresponsible. Now, O'Doherty and colleagues (page 95) extend the idea that the OFC is critical in forming associations between stimuli and their rewarding or punishing outcomes. Normal human subjects participated in a gambling task while they were in an fMRI scanner. Using a sophisticated event-related design, the authors were able to measure an increase in the activity of the lateral OFC related to the subjects' receipt of punishment (after selecting a stimulus that caused them to lose money; red) and deactivation following reward. The authors recorded the converse pattern in the medial OFC (activation following reward, blue; deactivation following punishment). Therefore, reward and punishment may be processed in distinct subregions of the OFC. Furthermore, the magnitude of activation correlated with the magnitude of the reward or punishment. These results may help to explain why patients with OFC damage seem to be unable to represent the magnitudes of gain or loss, and thus have difficulty judging whether particular decisions are advantageous based on previous experience.