A model of asymmetric contributions to the control of different subcomponents of approach- and withdrawal-related emotion and psychopathology is presented. Two major forms of positive affect are distinguished. An approach-related form arises prior to goal attainment, and another form follows goal attainment. The former is hypothesized to be associated with activation of the left prefrontal cortex. Individual differences in patterns of prefrontal activation are stable over time. Hypoactivation in this region is proposed to result in approach-related deficits and increase an individual's vulnerability to depression. Data in support of these proposals are presented. The issue of plasticity is then considered from several perspectives. Contextual factors are superimposed upon tonic individual differences and modulate the magnitude of asymmetry. Pharmacological challenges also alter patterns of frontal asymmetry. A diverse array of evidence was then reviewed that lends support to the notion that these patterns of asymmetry may be importantly influenced by early environmental factors that result in enduring changes in brain function and structure.