The adequate integration of reward- and decision-related information provided by the environment is critical for behavioral success and subjective well being in everyday life. Functional neuroimaging research has already presented a comprehensive picture on affective and motivational processing in the healthy human brain and has recently also turned its interest to the assessment of impaired brain function in psychiatric patients. This article presents an overview on neuroimaging studies dealing with reward processing and decision-making by combining most recent findings from fundamental and clinical research. It provides an outline on the neural mechanisms guiding context-adequate reward processing and decision-making processes in the healthy brain, and also addresses pathophysiological alterations in the brain's reward system that have been observed in substance abuse and mood disorders, two highly prevalent classes of psychiatric disorders. The overall goal is to critically evaluate the specificity of neurophysiological alterations identified in these psychiatric disorders and associated symptoms, and to make suggestions concerning future research.