The parasympathetic component of the autonomic nervous system plays an important role in the physiological regulation of cardiac function by exerting significant influence over the initiation as well as propagation of electrical impulses, in addition to being able to regulate contractile force. These effects are mediated in whole or in part through changes in ion channel activity that occur in response to activation of M(2) muscarinic cholinergic receptors following release of the neurotransmitter acetylcholine. The coupling of M(2) receptor activation to most changes in cardiac ion channel function can be explained by one of two general paradigms. The first involves direct G protein-dependent regulation of ion channel activity. The second involves indirect regulation of ion channel activity through modulation of cAMP-dependent responses. This review focuses on recent advances in our understanding of the mechanisms by which M(2) muscarinic receptor activation both inhibits and facilitates cAMP-dependent ion channel responses in the heart.