This article reviews the current understanding of the pathophysiology and clinical spectrum of heart failure. A cascade of hemodynamic and neurohormonal derangements result from a decrease in ventricular performance or cardiac output. Because neurohormonal activation has become a target for intervention in heart failure, the role of selected systems (sympathetic nervous, renin–angiotensin–aldosterone) and of natriuretic peptides is detailed. The spectrum (from compensated to acute decompensated) within which congestive heart failure patients present is reviewed, with special attention paid to the intermediate, transitional group of patients, who pose unique diagnostic and therapeutic challenges. Given these variable presentations, there is an obligation to tailor therapy accordingly.