Current heart failure rationales bear little resemblance to the pump failure model that prevailed in the 1970s, prompting prescriptions of digitalis to potentiate myocardial contractility and diuretics to decrease fluid retention. First, the 1980s focused on the feature of diffuse vasoconstriction and added vasodilators to the therapeutic regimen. Then a conceptual leap in the 1990s revealed the role of regulatory system hyperactivity, inspiring a range of renin-angiotensin-aldosterone and adrenergic system modulators with multifaceted and still unexhausted pharmacodynamic potential. Models, medicines, and an increasing wealth of devices have since driven each other forward to create the current plethora of complementary rationales. The macroscopic ventricular remodeling responsible for deteriorating ventricular dysfunction is related to microscopic disruption of the connective tissue matrix, since both features respond to angiotensin-converting enzyme therapy. Other models, each with an actual or, more often, potential therapeutic correlate, include the early role of diastolic dysfunction, ventricular desynchronization, the contribution of myocardial small vessel and endothelial disease revealed in hypertensive and diabetic heart failure, and the critical impact of cardiomyopathy genes and their differential expression depending on clinical circumstance. Unfortunately, these interdigitating narratives have yet to be generally mirrored in a seamless system of efficient heart failure care...