Dilated cardiomyopathy is a disease characterized by enlargement of the chambers of the heart and a decrease in contractility of the heart muscle. The process involves several alterations in proteins involved in cyclic adenosine monophosphate (cAMP) generation that result in a decrease in intracellular cAMP content per unit of adrenergic stimulation in cardiac myocytes. A fundamental question is whether these changes constitute a pathologic mechanism that contributes to chamber enlargement and hypocontractility or a compensatory adaptation that protects the heart from the adverse effects of increased catecholamine stimulation. Clinical studies in humans suggest that the latter effect may be more important. Studies in animal models, however, make the picture more complex: changes in cAMP-mediated signaling can have different effects depending on the specific protein whose expression or function is altered and the setting in which the alteration occurs. It may be that dilated cardiomyopathy represents a collection of different diseases in which alterations in cAMP-mediated signaling have different roles in the pathophysiology of the disease, and, furthermore, that changes in the phosphorylation of individual substrates of cAMP-dependent protein kinase may be either beneficial or harmful. Identifying differences among patients with dilated cardiomyopathy with respect to the role of altered cAMP-mediated signaling in their pathology, and identifying the "good" and "bad" substrates of cAMP-dependent protein kinase, are important areas for further research.