The cAMP pathway is of cardinal importance for heart physiology and pathology. The spatial organization of the various components of the cAMP pathway is thought to allow the segregation of functional responses triggered by the different neuromediators and hormones that use this pathway. PDEs (phosphodiesterases) hydrolyse cAMP (and cGMP) and play a major role in this process by preventing cAMP diffusion to the whole cytosol and inadequate target activation. The development of olfactory cyclic nucleotide-gated channels to directly monitor cAMP beneath the plasma membrane in real time allows us to gain new insights into the molecular mechanisms responsible for cAMP homoeostasis and hormonal specificity in cardiac cells. The present review summarizes the recent results we obtained using this approach in adult rat ventricular myocytes. In particular, the role of PDEs in the maintenance of specific cAMP signals generated by beta-adrenergic receptors and other G(s)-coupled receptors will be discussed.