Bipolar disorder is clinically characterized by fluctuating affect, and neuropsychologically by impairment in executive functions. Such phenomena are consistent with the centrality of emotional dysregulation and impulsivity to bipolar disorder. They are also consistent with a key role for prefrontal-subcortical (striatal-thalamic) and associated limbic circuitry in its mediation. Furthermore, there is growing data on the cellular mechanisms contributing to neuronal vulnerability in this mediating circuitry.