Affective neuroscience is a new emerging doctrine in the brain sciences, which studies the neurobiological correlates of motivation and emotion. The research reported in this thesis starts with discussing empirical studies on the lateralized involvement of the prefrontal cortex in affective processing. Next, the involvement of the parietal cortex, the cerebellum and their functional connectivity to the prefrontal cortex in affective processing will be examined. In addition, it will be argued that motivation and emotion are implemented in multiple and functionally interconnected brain regions. Furthermore, a heuristic working model will be presented, which does not only provide a theoretical basis for testing new hypotheses in affective neuroscientific research, but also for the clinical application of magnetic brain stimulation in the treatment of depression. The current thesis provides novel insights into the biological mechanisms of affectie processing, evidenced from electrophysiological, repetitive transcranial magnetic stimulation, endocrinological and behavioral studies.