Extensive clinical experience and research suggest that a cortico-limbic-subcortico-thalamic-ponto-cerebellar network plays a significant role in the expression of human emotions. This network includes specific cerebral, cerebellar, and brainstem areas and their multiple projections/pathways, with activity modulated through serotonergic, dopaminergic, glutamatergic, and possibly sigma receptor neurotransmitter systems. Disruptions of regulatory and inhibitory mechanisms in the structure and function of this network likely constitute a pathophysiological basis for the crying and laughing episodes characteristic of involuntary emotional expression disorder. Pharmacologic interventions targeting the neurochemical modulators of the emotional expression systems may afford opportunities for symptom control among persons affected by this disorder.