In this chapter, we review some of the research on the psychophysiological correlates of personality and social behavior that has been carried out in our laboratory and others, with specific emphasis on depression. Much of the research described is based on a model that stresses the importance of individual differences in the likelihood of expressing and modulating different emotions. There are individuals whose modal response to mild stress or novelty is one of approach and positive emotions, whereas other individuals display withdrawal responses and negative emotions. There are also individual differences within these groups in the intensity of emotion expression and in the ability to modulate expression. In this model, differences in the tendency to express either approach (positive) or withdrawal (negative) patterns in response to stress or novelty are fundamental to the motivational core of individuals. These differences are seen as being subsumed by different brain systems, with the tendency to express negative emotions and withdrawal organized within the right hemisphere and the tendency to express positive emotions and approach-related behaviors organized within the left hemisphere. Individual differences in the patterning of hemispheric activation may thus reflect individual differences in emotion regulation strategies, which may, in turn, determine vulnerability to affective disorders such as depression.