Heart failure is characterized by elevated circulating catecholamine levels and extensive abnormalities in β-adrenergic receptor signaling. Under physiological conditions, sympathetic modulation via catecholamines induces positive inotropic, chronotropic and lusitropic responses. Well established in heart failure patients is a pronounced activation of the sympathetic system, accompanied by downregulation and desensitization of β-adrenergic receptors, leading to a markedly diminished β-adrenergic contractile response. In this review, we will discuss the normal β-adrenergic receptor signaling pathway in the heart and focus on the pathphysiological alterations of β-adrenergic receptor signaling and contractile proteins in heart failure.