The recent literature on the involvement of cholinergic muscarinic mechanisms and adrenergic/cholinergic balance in affective disorders is reviewed and integrated with the older literature. There is strong evidence supporting the presence of exaggerated responses (behavioral, neuroendocrine, sleep) to cholinergic agents in affective disorder patients relative to normal controls and certain other psychiatric patients. There is also some, albeit less, conclusive evidence that these exaggerated responses may occur in euthymic individuals with a history of affective disorders, or in children at risk for development of affective disorders. Despite these promising results, suggesting a role for acetylcholine in the genetics of the affective disorders, further work in biochemistry and genetics is needed to link specific muscarinic receptors or other cholinergic variables to affective illness.