Antiadrenergic treatment is currently an emerging and very promising approach to the treatment of chronic heart failure. Although the adrenergic nervous system can be pharmacologically inhibited at multiple levels, it is the use of receptor-blocking agents that has generated the most interest and provided the most data for the "proof of concept" of this approach. In part because antiadrenergic treatment of chronic heart failure has developed in an atmosphere in which it was initially considered to be contraindicated (i.e., before Phase III clinical trials could be initiated), a large body of hypothesis-driven basic and clinical investigation was required to define the overall rationale and demonstrate feasibility. This article will review these data and propose a single primary mechanism of action to explain most of the clinical benefits of these agents.