Adrenergic receptors transduce signals through the G proteins to regulate cardiac function. The catecholamines, via &agr;- and &bgr;-adrenergic receptor (&bgr;-AR) stimulation, may play a role in the development of heart failure. Norepinephrine and isoproterenol can induce cardiac myocyte apoptosis.In vitrostudies suggest that &agr;-, &bgr;1-, and &bgr;2-adrenergic pathways differentially regulate cardiac myocyte apoptosis. The stimulation of &bgr;1-AR leads to cyclic AMP–dependent apoptosis, whereas that of the &bgr;2-AR elicits concurrent apoptosis and survival signals in cardiac myocytes coupled to Gsprotein. Overexpression of &agr;1-adrenergic receptors does not induce apoptosis in wild-type mice. In contrast, the heart failure observed in some murine models has to be related to an enhanced &bgr;-AR kinase expression. These recent advances make it possible to understand the beneficial effects of &bgr;-blockers in the treatment of chronic heart failure and provide novel therapeutic modalities through the stimulation of &bgr;2-ARs or the inhibition of &bgr;-AR kinase expression.